NOVEL COMPOSITION FOR TREATING METABOLIC SYNDROME AND OTHER CONDITIONS

• US 20120183600A1
• Filed: 01/04/2012
• Published: 07/19/2012
• Est. Priority Date: 01/16/2007
• Status: Abandoned Application

• Current Assignee: Chien-Hung Chen
• Original Assignee: Chien-Hung Chen
• Inventors: Chen, Chien-Hung
• Application Number:
  US13/343,634
• Publication Number:
  US 20120183600A1
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/4045 Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
• CPC Class Codes: A61K 31/60 Salicylic acid; Derivatives thereof
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

The invention relates to a composition that includes a first agent selected from the group consisting of an oxidative phosphorylation inhibitor, an ionophore, and an adenosine 5′-monophosphate-activated protein kinase (AMPK) activator; a second agent that possesses anti-inflammatory activity; and a third agent that possesses serotonin activity.

Claims

1. A composition comprising:

(a) an effective amount of a first agent selected from the group consisting of an oxidative phosphorylation inhibitor, an ionophore, and an adenosine 5′

-monophosphate-activated protein kinase (AMPK) activator;

(b) an effective amount of a second agent that possesses anti-inflammatory activity; and

(c) an effective amount of a third agent that possesses or maintains serotonin activity.

7. The composition of claim 1 wherein the first agent is an adenosine 5′

-monophosphate-activated protein kinase (AMPK) activator.

8. The composition of claim 7 wherein the adenosine 5′

-monophosphate-activated protein kinase (AMPK) activator is selected from the group consisting of;

(1) metformin;

(2) phenformin;

(3) buformin;

(4) AICAR;

(5) a thienopyridone;

(6) resveratrol;

(7) nootkatone;

(8) thiazole;

(9) adiponectin;

(10) 2-deoxyglucose;

(11) AAPDs;

(12) adiponectin variant polypeptides;

(13) catechins;

(14) trans-10, cis-12 conjugated linoleic acid;

(15) a corydaline-related compound selected from the group consisting of corydaline, corlumidin, (+)-corlumidin, corypalmine, 14R—

H-corypalmine, tetrahydropalmatine, 14R-(+)-tetrahydropalmatine, 14R,13S-(+)-corydaline, bicuculline, d-(+) -bicuculline, egenine, and +-egenine;

(16) a dithiolethione;

(17) an inhibitor or antagonist of DNA-dependent protein kinase catalytic subunit (DNA-PKcs);

(18) a small interfering RNA (siRNA) that can inhibit the expression and/or translation of DNA-PKcs;

(19) a fibrate selected from the group consisting of bezafibrate, ciprofibrate, fenofibrate, clofibrate, and gemfibrozil;

(20) GW2974 (N4-(1-benzyl-1H-indazol-5-yl)-N6,N6-dimethyl-pyrido-[3,4-d]-pyrimidine-4,6-diamine);

(21) honokiol;

(22) leptin;

(23) LKB1 (serine/threonine kinase

     11);

(24) obovatol (4′

,5-diallyl-2,3-dihydroxybiphenyl ether);

(25) a thiazolidinedione selected from the group consisting of pioglitazone and related thiazolidinediones, including rosiglitazone and rosiglitazone maleate;

(26) a variant adiponectin peptide having one or more mutations at amino acid positions 109-229 of wild-type adiponectin and having at least threefold increased solubility when compared to wild-type adiponectin;

(27) a butyrate compound selected from a butyrate salt and a butyrate ester; and

(28) a quinoxalinedione derivative; and

the salts, solvates, analogues, congeners, bioisosteres, hydrolysis products, metabolites, precursors, and prodrugs thereof.

9. The composition of claim 8 wherein the adenosine 5′

-monophosphate-activated protein kinase (AMPK) activator is selected from the group consisting of metformin, phenformin, buformin, and the salts thereof, and a butyrate compound selected from the group consisting of a butyrate salt and a butyrate ester.

11. The composition of claim 1 wherein the second agent that possesses anti-inflammatory activity is selected from the group consisting of a steroidal anti-inflammatory drug and a non-steroidal anti-inflammatory drug.

13. The composition of claim 11 wherein the second agent that possesses anti-inflammatory activity is a steroidal anti-inflammatory drug and wherein the steroidal anti-inflammatory drug is selected from the group consisting of:

(1) hydrocortisone;

(2) cortisone;

(3) beclomethasone;

(4) betamethasone;

(5) dexamethasone;

(6) prednisone;

(7) methylprednisolone;

(8) triamcinolone;

(9) fluocinolone;

(10) fludrocortisone;

(11) hyaluronic acid 6-methylprednisolone ester;

(12) rimexolone;

(13) deflazacort, (14) prednisolone;

(15) ORG6632 (21-chloro-9α

-11β

-hydroxy-16α

,17α

-dimethylpregna-1,4-diene-3,20-dione);

(16) 21-acetoxypregnenolone;

(17) alclometasone;

(18) algestone;

(19) amcinonide;

(20) azulfidine;

(21) budesonide;

(22) chloroprednisone;

(23) clobetasol;

(24) clocortolone;

(25) cloprednol;

(26) corticosterone;

(27) desonide;

(28) desoximetasone;

(29) desoxycorticosterone;

(30) diflorasone;

(31) difluprednate;

(32) enoxolone;

(33) fluazacort;

(34) flucloronide;

(35) flumethasone;

(36) flunisolide;

(37) fluocortolone;

(38) fluorometholone;

(39) fluprednidene;

(40) fluprednisolone;

(41) fluticasone;

(42) halcinonide;

(43) halobetasol;

(44) halometasone;

(45) hydrocortamate;

(46) medrysone;

(47) meprednisone;

(48) mometasone;

(49) paramethasone;

(50) prednicarbate;

(51) prednival;

(52) prednylidene;

(53) tixocortol;

(54) clobetasone;

(55) cortivazol;

(56) diflucortolone;

(57) fluocinolone;

(58) fluocortin;

(59) fluperolone;

(60) formocortal;

(61) halopredone;

(62) mazipredone;

(63) 6α

,9α

-difluoro-17α

-[(2-furanylcarbonyl)oxy]-11β

-hydroxy-16α

-methyl-3-oxoandrosta-1,4-diene-17β

-carbothioic acid S-fluoromethyl ester;

(64) 6α

,9α

-difluoro-11β

-hydroxy-16α

-methyl-3-oxo-17α

-propionyloxy-androsta-1,4-diene-17β

-carbothioic acid S-(2-oxo-tetrahydrofuran-3S-yl)ester;

(65) rofleponide;

(66) ciclesonide;

(67) butixocort;

(68) RPR-106541 (20R-16α

,17α

-[butylidenebis(oxy)]-6α

,9α

-difluoro-11β

-hydroxy-17β

-(methylthio)androsta-4-en-3-one);

(69) ST-126 (9-Fluoro-11β

,17,21-trihydroxy-16α

-methyl-1,4-pregnadiene-3,20-dione 21-cyclohexanecarboxylate cyclopropanecarboxylate);

(70) flurandrenolide;

(71) 9α

-fluoro-11β

,17α

-dihydroxy-21-methoxy-16α

-methylpregna-1,4-diene-3,20-dione;

(72) 9α

-fluoro-11β

,17α

-dihydroxy-21-benzyl oxy-16α

-methyl pregna-1,4-diene-3,20-dione;

(73) 9α

-fluoro-11β

,17α

-dihydroxy-21-(2-methoxyethoxy)methoxy-16α

-methylpregna-1,4-diene-3,20-dione;

(74) 9α

-fluoro-11β

,17α

-dihydroxy-21-(2-hydroxylethoxy)-16α

-methylpregna-1,4-diene-3,20-dione;

(75) 9α

-fluoro-11β

,17α

-dihydroxy-21-(methylthiomethoxy)-16α

-methylpregna-1,4-diene-3,20-dione (76) 9α

-fluoro-11β

,17α

-dihydroxy-21-(methoxy)methoxy-16α

-methylpregna-1,4-diene-3,20-dione;

(77) 9α

-fluoro-11β

,17α

-dihydroxy-Δ

₂₀-ethoxy-21-ethoxy-16α

-methylpregna-1,4-diene-3,20-dione;

(78) 9α

-fluoro-11β

,17α

-dihydroxy-21-ethoxy-16α

-methylpregna-1,4-diene-3,20-dione;

(79) 9α

-fluoro-11β

,17α

-dihydroxy-21-allyloxy-16α

-methylpregna-1,4-diene-3,20-dione;

(80) 9α

-fluoro-11β

,17α

-dihydroxy-21-cyclopropylmethoxy-16α

-methylpregna-1,4-diene-3,20-dione;

(81) 9α

-fluoro-11β

,17α

-dihydroxy-21-allyl-21-allyloxy-16α

-methyl-1,4-diene-3,20-dione;

(82) 9α

-fluoro-11β

,17α

-hydroxy-21-isopropyloxy-16α

-methylpregna-1,4-diene-3,20-dione;

(83) 9α

-fluoro-11β

-propionoxy-17α

-hydroxy-21-methoxy-16α

-methyl pregna-3,20-dione; and

(84) 9α

-fluoro-11β

-17α

-diacetoxy-21-methoxy-16α

-methylpregna-1,4-diene-3,20-dione; and

the esters, acetonides, benetonides, furetonides, salts, solvates, analogues, congeners, bioisosteres, hydrolysis products, metabolites, precursors, and prodrugs thereof.

15. The composition of claim 11 wherein the second agent that possesses anti-inflammatory activity is a non-steroidal anti-inflammatory drug and wherein the non-steroidal anti-inflammatory drug is selected from the group consisting of:

(1) A183827;

(2) ABT963;

(3) aceclofenac;

(4) acemetacin;

(5) acetaminophen;

(6) acetylsalicylic acid;

(7) ACP;

(8) actarit;

(9) AHR10037;

(10) AHR15010;

(11) alclofenac;

(12) alminoprofen;

(13) amfenac;

(14) ampiroxicam (15) amtolmetin guacil;

(16) apazone;

(17) araprofen;

(18) atliprofen methyl ester;

(19) AU8001;

(20) azapropazone;

(21) bendazac;

(22) benoxaprofen;

(23) benzydamine;

(24) benzydamine flufenamate;

(25) bermoprofen;

(26) benzpiperylon;

(27) BF388;

(28) BF389;

(29) BIRL790;

(30) BMS347070;

(31) bromfenac;

(32) bucloxic acid;

(33) bumadizone;

(34) butibufen;

(35) BW4C;

(36) BW755C;

(37) C53;

(38) C73;

(39) C85;

(40) carprofen;

(41) CBS1108;

(42) celecoxib;

(43) CGS25997;

(44) CHF2003;

(45) chlorobiphenyl;

(46) choline magnesium trisalicylate;

(47) CHX108;

(48) CI959;

(49) cimicoxib;

(50) cinmetacin;

(51) cinnoxicam;

(52) clidanac;

(53) clofezone;

(54) clonixin;

(55) clopirac;

(56) CLX1205;

(57) COX-2 inhibitors;

(58) CP331;

(59) CS502;

(60) CS706;

(61) D1367;

(62) darbufelone;

(63) deracoxib;

(64) dexibuprofen;

(65) dexibuprofen lysine;

(66) dexketoprofen;

(67) DFP;

(68) DFU;

(69) diclofenac sodium;

(70) diclofenac potassium;

(71) diflunisal;

(72) DP155;

(73) DRF4367;

(74) droxicam;

(75) E5110;

(76) E6080;

(77) E6087;

(78) eltenac;

(79) enfenamic acid;

(80) epirizole;

(81) ER34122;

(82) esflurbiprofen;

(83) ethenzamide;

(84) etodolac;

(85) etofenamate;

(86) etoricoxib;

(87) F025;

(88) FCE20696;

(89) felbinac;

(90) felbinac ethyl;

(91) fenbufen;

(92) fenclofenac;

(93) fenclozic acid;

(94) fenclozine;

(95) fendosal;

(96) fenoprofen;

(97) fentiazac;

(98) fepradinol;

(99) feprazone;

(100) filenadol;

(101) flobufen;

(102) florifenine;

(103) flosulide;

(104) flubichin methanesulfonate;

(105) flufenamic acid;

(106) flufenisal;

(107) flunixin;

(108) flunoxaprofen;

(109) fluprofen;

(110) fluproquazone;

(111) flurbiprofen;

(112) FPL62064;

(113) FR111142;

(114) FR122047;

(115) FR123826;

(116) FR140423;

(117) FR188582;

(118) FS205397;

(119) furofenac;

(120) GR80907;

(121) GR129574A;

(122) GR253035;

(123) GW406381;

(124) HAI105;

(125) HAI106;

(126) HCT2035;

(127) HGP12;

(128) 11N3392;

(129) HP977;

(130) HX0835;

(131) HYAL AT2101;

(132) ibufenac;

(133) ibuprofen;

(134) ibuproxam-beta-cyclodextrin;

(135) icodulinum;

(136) IDEA070;

(137) iguratimod;

(138) imrecoxib;

(139) indomethacin;

(140) indoprofen;

(141) IP751;

(142) IRA378;

(143) isofezolac;

(144) isoxepac;

(145) isoxicam;

(146) IX207887;

(147) KC764;

(148) ketoprofen;

(149) ketorolac;

(150) L652343;

(151) L745337;

(152) L748731;

(153) L752860;

(154) L651392;

(155) L663536;

(156) L761066;

(157) L768277;

(158) L776967;

(159) L783003;

(160) L784520;

(161) L791456;

(162) L804600;

(163) L818571;

(164) LAS33815;

(165) LAS34475;

(166) licofelone;

(167) LM4108;

(168) lobuprofen;

(169) lornoxicam;

(170) lonazolac;

(171) loxaprofen;

(172) lumaricoxib;

(173) LY221608;

(174) LY269415;

(175) mabuprofen;

(176) meclofenamic acid;

(177) meclofenamate sodium;

(178) mefenamic acid;

(179) meloxicam;

(180) mercaptoethylguanidine;

(181) mesaclazone;

(182) mesoporphyrin;

(183) metoxibutropate;

(184) miroprofen;

(185) mofebutazone;

(186) mofezolac;

(187) morazone;

(188) MX 1094;

(189) nabumetone;

(190) naproxen sodium;

(191) naproxen sodium/metoclopramide;

(192) NCX1101;

(193) NCX284;

(194) NCX285;

(195) NCX4016;

(196) NCX4215;

(197) NCX530;

(198) nepafanac;

(199) niflumic acid;

(200) nimesulide;

(201) nitric oxide-based NSAIDs;

(202) nitrofenac;

(203) nitroflurbiprofen;

(204) nitronaproxen;

(205) NS398;

(206) ocimum sanctum oil;

(207) olsalazine;

(208) ONO3144);

(209) orpanoxin;

(210) oxaceprol;

(211) oxaprozin;

(212) oxindanac;

(213) oxpinac;

(214) oxycodone/ibuprofen;

(215) oxyphenbutazone;

(216) P10294;

(217) P54;

(218) P8892;

(219) pamicogrel;

(220) parcetasal;

(221) parecoxib;

(222) parsalmide;

(223) PD138387;

(224) PD145246;

(225) PD164387;

(226) pelubiprofen;

(227) pemedolac;

(228) phenylbutazone;

(229) pirazolac;

(230) piroxicam;

(231) piroxicam beta-cyclodextrin;

(232) piroxicam pivalate;

(233) pirprofen;

(234) pranoprofen;

(235) prinomide;

(236) proglumetacin;

(237) resveratrol;

(238) R-ketoprofen;

(239) R-ketorolac;

(240) Ro323555;

(241) rofecoxib;

(242) RP54745;

(243) RP66364;

(244) RU43526;

(245) RU46057;

(246) RU54808;

(247) RWJ63556;

(248) S19812;

(249) S33516;

(250) salicin;

(251) salicylamide;

(252) salicylsalicylic acid;

(253) satigrel;

(254) SC236;

(255) SC57666;

(256) SC58125;

(257) SC58451;

(258) SD8381;

(259) seprilose;

(260) SFPP;

(261) SKF105809;

(262) SKF86002;

(263) sodium salicylate;

(264) sudoxicam;

(265) sulfasalazine;

(266) sulindac;

(267) suprofen;

(268) SVT2016;

(269) T3788;

(270) TA60;

(271) talmetacin;

(272) talniflumate;

(273) tazofelone;

(274) tebufelone;

(275) tenidap;

(276) tenoxicam;

(277) tepoxalin;

(278) tiaprofenic acid;

(279) tiaramide;

(280) tilmacoxib;

(281) tilnoprofen arbamel;

(282) tinoridine;

(283) tiopinac;

(284) tioxaprofen;

(285) tolfenamic acid;

(286) tolmetin;

(287) triflusal;

(288) tropesin;

(289) TY10222;

(290) TY10246;

(291) TY10474;

(292) UR8962;

(293) U91502;

(294) ursolic acid;

(295) valdecoxib;

(296) WAY120739;

(297) WY28342;

(298) WY41770;

(299) WY46135;

(300) ximoprofen;

(301) YS134;

(302) zaltoprofen;

(303) ZD2138;

(304) zidometacin;

(305) zomepirac;

(306) AA961;

(307) acetaminosalol;

(308) AD1590;

(309) AFP802;

(310) aloxiprin;

(311) amfenac sodium;

(312) aminopropylon;

(313) aminopyrine;

(314) amoxiprin;

(315) anirolac;

(316) anitrazafen;

(317) antrafenine;

(318) 2-arylpropionic acids;

(319) azulene sodium sulfonate;

(320) baicalein;

(321) bendazac lysinate;

(322) benorylate;

(323) biphenyl aspirin;

(324) BPPC;

(325) bromfenac sodium;

(326) broperamole;

(327) bufexamac;

(328) bufezolac;

(329) BW540C;

(330) caffeic acid;

(331) calcium acetylsalicylate;

(332) Chinoin 127;

(333) choline salicylate;

(334) cicloprofen;

(335) cinchophen;

(336) cintazone;

(337) cipamfylline;

(338) clobuzarit;

(339) clometacin;

(340) clonixeril;

(341) cloximate;

(342) CN100;

(343) 4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide;

(344) cyclooxygenase-1 inhibitors;

(345) delmetacin;

(346) dexindoprofen;

(347) diaryl-5-oxygenated-2-(5H)-furanone;

(348) 2,4-dichlorobenoxaprofen;

(349) difenpiramide;

(350) diflumidone sodium;

(351) 2-(3,5-difluorophenyl)-3-[4-(methylsulfonyl)phenyl]-2-cyclopenten-1-one);

(352) diftalone;

(353) dimethylisopropylazulene;

(354) 5,5-dimethyl-3-isopropyloxy-4-(4′

-methylsulfonylphenyl)-2(5H)-furanone;

(355) dimethyl sulfoxide;

(356) DKA9;

(357) DUP697;

(358) EB382;

(359) eicosatriynoic acid;

(360) emorfazone;

(361) enolicam;

(362) ethyleneglycol salicylate;

(363) F1044;

(364) fenamates;

(365) fenamole;

(366) fenbuprofen;

(367) fenclorac;

(368) fenflumizole;

(369) fenoprofen calcium;

(370) floctafenine;

(371) flunixin meglumine;

(372) flurbiprofen axetil;

(373) fosfosal;

(374) furcloprofen;

(375) glafenine;

(376) glucametacin;

(377) GP53633;

(378) 5(S)-1-1E1E;

(379) 5-RETE lactone;

(380) ibuprofen aluminum;

(381) ibuprofen piconol;

(382) ibuproxam;

(383) imidazole salicylate;

(384) indometacin farnesil;

(385) indomethacin sodium trihydrate;

(386) indoxole;

(387) intrazole;

(388) ITC1;

(389) ITF182;

(390) JTE522;

(391) KB1043;

(392) KC8973;

(393) ketophenylbutazone;

(394) ketorolac tromethamine;

(395) KME4;

(396) LA2851;

(397) 5-lipoxygenase inhibitors;

(398) lofemizole;

(399) lonazolac calcium;

(400) lotifazole;

(401) lysine acetylsalicylate;

(402) lysine clonixinate;

(403) LU20884;

(404) M7074;

(405) magnesium salicylate;

(406) mefenamic acid aluminum;

(407) mesalamine;

(408) metamizole sodium;

(409) metazamide;

(410) metiazinic acid;

(411) 6-methoxy-2 naphthylacetic acid;

(412) MG18311;

(413) mixed PDE3/PDE4 inhibitors;

(414) morniflumate;

(415) morpholine salicylate;

(416) MR714;

(417) MR897;

(418) N-acetyl-5-aminosalicylic acid;

(419) 1-naphthyl salicylate;

(420) N-[2-(cyclohexyloxy)-4-nitrophenyl]methanesulfonamide;

(421) neocinchophen;

(422) nictindole;

(423) nifenazone;

(424) 2-(2-nitroxy)-butyl 2-acetoxybenzoate;

(425) 2-(2-nitroxymethyl)phenyl 2-acetoxybenzoate;

(426) NO164;

(427) NPPB;

(428) N-(2-pyridyl)-2-methyl-4-cinnamoyloxy-2H-1,2-benzothiazine-3-carboxamido 1,1-dioxide;

(429) o-(acetoxyphenyl)hept-2-ynyl sulfide (APHS);

(430) olsalazine oxaceprol;

(431) olsalazine sodium;

(432) oxametacin;

(433) oxapadol;

(434) oxicams;

(435) oxyphenthatrazone;

(436) paranylene;

(437) peroxisal;

(438) peroxisal citrate;

(439) phenazone;

(440) phenidone;

(441) phenyl O-acetylsalicylate;

(442) pifoxime;

(443) piketoprofen;

(444) pimeprofen;

(445) piprofen;

(446) piroxicam cinnamate;

(447) proglumetacin maleate;

(448) propyphenazone;

(449) proquazone;

(450) protizinic acid;

(451) QZ16;

(452) R830;

(453) R-enantiomers of acrylacetic acids;

(454) R-enantiomers of arylpropionic acids;

(455) R-enantiomers of thiazinecarboxamides;

(456) RS2131;

(457) RS57067;

(458) RU16029;

(459) salicylamide O-acetic acid;

(460) SC560;

(461) SCR152;

(462) sermetacin;

(463) sodium acetylsalicylate;

(464) sodium thiosalicylate;

(465) sulindac sulfide;

(466) suxibutazone;

(467) T614;

(468) TAI901;

(469) tesicam;

(470) tetrydamine;

(471) thromboxane inhibitors;

(472) tiflamizole;

(473) timegadine;

(474) tinoridine hydrochloride;

(475) tomoxiprol;

(476) triethanolamine salicylate;

(477) triflumidate;

(478) trimethazone;

(479) TVX960;

(480) TVX2706;

(481) TZI615;

(482) U60257;

(483) ufenamate;

(484) vedaprofen;

(485) WY23205;

(486) xenbucin; and

(487) zileuton; and

the salts, solvates, analogues, congeners, bioisosteres, hydrolysis products, metabolites, precursors, and prodrugs thereof.

16. The composition of claim 15 wherein the non-steroidal anti-inflammatory drug is selected from the group consisting of acetylsalicylic acid and the salts thereof.

17. The composition of claim 15 wherein the non-steroidal anti-inflammatory drug is selected from the group consisting of alminoprofen, araprofen, atliprofen methyl ester, benoxaprofen, bermoprofen, butibufen, carprofen, dexibuprofen, dexibuprofen lysine, dexketoprofen, esflurbiprofen, fenbufen, fenoprofen, flobufen, flunoxaprofen, fluprofen, flurbiprofen, ibuprofen, indoprofen, ketoprofen, lobuprofen, loxaprofen, mabuprofen, miroprofen, MX1094, naproxen sodium, naproxen sodium/metoclopramide, nitroflurbiprofen, nitronaproxen, oxaprozin, oxycodone/ibuprofen, pelubiprofen, pirprofen, pranoprofen, R-ketoprofen, suprofen, tiaprofenic acid, tilnoprofen arbamel, tioxaprofen, ximoprofen, zaltoprofen, cicloprofen, dexindoprofen, 2,4-dichlorobenoxaprofen, fenbuprofen, fenoprofen calcium, flurbiprofen axetil, furcloprofen, ibuprofen aluminum, ibuprofen piconol, piketoprofen, pimeprofen, piprofen, and vedaprofen, and the salts thereof.

18. The composition of claim 15 wherein the non-steroidal anti-inflammatory drug is selected from the group consisting of aceclofenac, acemetacin, alclofenac, amfenac, bendazac, bromfenac, clidanac, clopirac, CP331, diclofenac sodium, diclofenac potassium, eltenac, etodolac, felbinac, felbinac ethyl, fenclofenac, furofenac, HCT6015, HYAL AT2101, ibufenac, indomethacin, isofezolac, ketorolac, LM4108, lonazolac, mofezolac, NCX284, NCX285, NCX530, nepafanac, nitrofenac, oxindanac, pemedolac, pirazolac, R-ketorolac, sulindac, talmetacin, tiopinac, zidometacin, zomepirac, amfenac sodium, anirolac, bendazac lysinate, bromfenac sodium, bufexamac, bufezolac, clometacin, delmetacin, fenclorac, glucametacin, indometacin farnesil, indomethacin sodium trihydrate, ketorolac tromethamine, lonazolac calcium, oxametacin, proglumetacin maleate, and sermetacin, and the salts thereof.

19. The composition of claim 15 wherein the non-steroidal anti-inflammatory drug is selected from the group consisting of ampiroxicam, cinnoxicam, isoxicam, lornoxicam, meloxicam, piroxicam, piroxicam beta-cyclodextrin, piroxicam pivalate, sudoxicam, tenoxicam, enolicam, piroxicam cinnamate, and tesicam, and the salts thereof.

20. The composition of claim 15 wherein the non-steroidal anti-inflammatory drug is selected from the group consisting of benzydamine flufenamate, enfenamic acid, etofenamate, flufenamic acid, meclofenamic acid, meclofenamate sodium, mefenamic acid, tolfenamic acid, mefenamic acid aluminum, and ufenamate, and the salts thereof.

22. The composition of claim 15 wherein the non-steroidal anti-inflammatory drug is acetaminophen or a salt thereof.

24. The composition of claim 15 wherein the non-steroidal anti-inflammatory drug is selected from the group consisting of celecoxib, cimicoxib, deracoxib, etoricoxib, imrecoxib, lumiracoxib, parecoxib, rofecoxib, tilmacoxib, and valdecoxib, and the salts thereof.

26. The composition of claim 15 wherein the non-steroidal anti-inflammatory drug is nimesulide or a salt thereof.

27. The composition of claim 1 wherein the third agent that possesses or maintains serotonin activity is selected from the group consisting of serotonin, a serotonergic compound, and a serotonin metabolite.

28. The composition of claim 27 wherein the third agent is serotonin or a salt thereof.

29. The compound of claim 27 wherein the third agent is selected from the group consisting of serotonin sulfate, a serotonin creatinine sulfate complex, and serotonin hydrochloride.

30. The composition of claim 27 wherein the third agent is a serotonergic compound selected from the group consisting of a serotonin transporter inhibitor, a serotonin receptor 1A antagonist, a serotonin receptor 2C modulator, a serotonin reuptake inhibitor, a serotonin and noradrenaline reuptake inhibitor, a serotonin dopamine antagonist, a monoamine reuptake inhibitor, a pyridazinone aldose reductase inhibitor, a stimulant of serotonin receptors, a stimulant of serotonin synthesis, and a serotonin agonist.

32. The composition of claim 27 wherein the third agent is a serotonin metabolite and wherein the serotonin metabolite is selected from the group consisting of 5-HIAA, melatonin, and the salts thereof.

33. The composition of claim 1 wherein the third agent is selected from the group consisting of:

(1) paroxetine;

(2) fluoxetine;

(3) fenfluramine;

(4) fluvoxamine;

(5) sertraline;

(6) imipramine;

(7) BVT933;

(8) DPCA37215;

(9) IK264;

(10) PNU22394 (6-methyl-1,2,3,4,5,6-hexahydro-azepino[4,5-b]indole);

(11) WAY161503 (8,9-dichloro-2,3,4,4a-tetrahydro-1H-pyrazino[1,2-a]quinoxalin-5(6H)-one hydrochloride);

(12) R-1065;

(13) YM348 ((2S)-1-(7-ethyl-1H-furo[2,3-g]indazol-1-yl)propan-2-amine);

(14) milnacipran;

(15) citalopram;

(16) desmethylsertraline (a metabolite of sertraline);

(17) norfluoxetine;

(18) desmethylcitalopram (a metabolite of citalopram);

(19) escitalopram;

(20) femoxetine;

(21) ifoxetine;

(22) cyanodothiepin;

(23) litoxetine;

(24) dapoxetine;

(25) nefazodone;

(26) cericlamine;

(27) trazodone;

(28) mirtazapine;

(29) indalpine;

(30) indeloxazine;

(31) sibutramine;

(32) zimeldine;

(33) (+)-N-[1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutyl}-N-methylamine;

(34) (+)-N-{1-[1-(4-chlorophenyl)cyclobutyl-3-methylbutyl}-N-methylamine;

(35) (+)-1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutylamine;

(36) (+)-N-{1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutyl}-N;

(37) (+)-N-{1-[1-(4-chlorophenyl)cyclobutyl}-3-methylbutyl-N,N-dimethylamine)N-dimethylamine;

(38) venlafaxine;

(39) O-desmethylvenlafaxine (a metabolite of venlafaxine);

(40) clomipramine;

(41) desmethylclomipramine (a metabolite of clomipramine);

(42) buspirone;

(43) olanzapine;

(44) ziprasidone;

(45) ergoloid mesylates;

(46) pergolide mesylate;

(47) vitamin B1;

(48) vitamin B3;

(49) vitamin B6;

(50) biotin;

(51) S-adenosylmethionine;

(52) folic acid;

(53) folinic acid;

(54) ascorbic acid;

(55) magnesium;

(56) coenzyme Q10;

(57) piracetam;

(58) (+)-2,5-dimethoxy-4-iodoamphetamine;

(59) (+)-3,4-methylenedioxyamphetamine;

(60) (+)-N-[2-[4-[2,3-dihydro-2-(hydroxymethyl)-1,4-benzodioxin-5-yl]1-piperazinyl]-4-fluorobenzamide hydrochloride;

(61) (+)-norfenfluramine (a metabolite of fenfluramine);

(62) (3β

)-2,3-dihydrolysergene;

(63) (3β

)-2,3-dihydrolysergol;

(64) (3β

)-2,3-dihydro-methyllysergate;

(65) (3β

, 5β

, 8β

)-9,10-didehydro-2,3-dihydro-6-methyl-8-(2-pyridylthiomethyl)ergoline;

(66) (3β

, 5β

, 8β

)-9,10-didehydro-2,3-dihydro-6-methyl-8-(methylthiomethyl)ergoline;

(67) (3β

, 5β

, 8β

)-9,10-didehydro-2,3-dihydro-6-methyl-8-(phenylthiomethyl)ergoline;

(68) (3β

, 5β

, 8β

)-9,10-didehydro-2,3-dihydro-8-methyl-6-propylergoline;

(69) 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane;

(70) 1-(m-trifluoromethylphenyl)-piperazine;

(71) 2-(4-(4-(2-pyrimidinyl)1-piperazinyl-propyl)-1,2-benzoisothiazol-3-(2H)-one 1,1-dioxide hydrochloride;

(72) 2-methylserotonin;

(73) 3β

, 5β

, 8β

)-9,10-didehydro-2,3-dihydro-6-methylergoline-8-acetonitrile;

(74) zolmitriptan;

(75) 3 a,4,4a,6a,7,7a-hexahydro-2-[4-[4-(2-pyrimidinyl)-11-piperazinyl]butyl]-4,7-etheno-1H-cyclobutanoisoindole-1,3(2H)-dione dihydrochloride sesquihydrate;

(76) 3-butyl-9,9-dimethyl-7-[4-[4-(2-methoxyphenyl) 1-piperazinyl]butyl]-3,7-diazabicyclo[3,2,1]nonane-2,4,6,8-tetraone;

(77) 4,4-dimethyl-1-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]2,6-piperidinedione hydrochloride;

(78) 5-hydroxy-L-tryptophan;

(79) 5-methoxy-N,N-dimethyltryptamine;

(80) 6-[[3-[4[o-methoxyphenyl]-1-piperazinyl]propyl]-amino]-1,3-dimethyluracil;

(81) 8-[4-N-[4-(2-pyrimidinyl)-1-piperazinyl]-butyl]-8-azaspiro[4.5]-decane-7,9-dione hydrochloride;

(82) 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT);

(83) alniditan;

(84) almotriptan;

(85) 2-aminotetralin;

(86) bifeprunox;

(87) gepirone;

(88) BW723C86 (1-[5(2-thienylmethoxy)-1H-3-indolyl[propan-2-amine hydrochloride);

(89) cisapride;

(90) dihydroergotamine;

(91) D-lysergic acid diethylamide;

(92) donitriptan;

(93) eletriptan;

(94) frovatriptan;

(95) tegaserod;

(96) ipsapirone;

(97) L694247 (2-[5-[3-(4-methylsulphonylamino)benzyl-1,2,4-oxadiazol-5-yl]-1H-indol-3-yl]ethanamine);

(98) cinitapride;

(99) lesopitron;

(100) MCPP (m-chlorophenylpiperazine);

(101) methysergide;

(102) metoclopramide;

(103) MK-212 (6-chloro-2-(1-piperazinyl)pyrazine hydrochloride);

(104) mosapride;

(105) N,N-dimethyl-5-methoxytryptamine;

(106) N,N-dimethyltryptamine;

(107) N-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butylbicyclo[2.2.1]heptane-2,3-di-oxo-carboximide;

(108) naratriptan;

(109) norcisapride;

(110) phentermine;

(111) quipazine;

(112) prucalopride;

(113) rauwolscine;

(114) repinotan;

(115) rizatriptan;

(116) sumatriptan;

(117) tandospirone;

(118) 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine;

(119) tiaspirone;

(120) trifluoromethylphenylpiperazine;

(121) L-tryptophan;

(122) xaliproden;

(123) yohimbine;

(124) zacopride;

(125) zalospirone (126) mianserin;

(127) setiptiline;

(128) adatanserin;

(129) altanserin;

(130) benanserin;

(131) blonanserin;

(132) butanserin;

(133) cinanserin;

(134) eplivanserin;

(135) flibanserin (136) glemanserin;

(137) iferanserin;

(138) ketanserin;

(139) lidanserin;

(140) pelanserin;

(141) pruvanserin;

(142) ritanserin;

(143) seganserin;

(144) tropanserin;

(145) iloperidone;

(146) sertindole;

(147) EMR-62218;

(148) asenapine;

(149) zotepine;

(150) ocaperidone;

(151) APD125;

(152) AVE8488;

(153) pimavanserin;

(154) isocarboxazid;

(155) phenelzine;

(156) tranylcypromine;

(157) amitriptyline;

(158) clomipramine;

(159) N-(1-(1-methylethyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;

(160) N-(1-(2,2-dimethylethyppiperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;

(161) N-(1-pentylpiperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;

(162) N-(1-hexylpiperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;

(163) N-(1-cyclohexylpiperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;

(164) N-(1-cyclopentylpiperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide, (165) N-(1-cyclobutylpiperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;

(166) N-(1-cyclopropylpiperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;

(167) N-(1-(cyclopentylmethyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;

(168) N-(1-(cyclobutylmethyppiperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;

(169) N-(1-(cyclopropylmethyppiperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;

(170) N-(1-(2-hydroxyethyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;

(171) N-(1-(3-hydroxypropyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;

(172) N-((4-Methylphenyl)methyl)-N-(piperidin-4-yl)-N′

-phenylmethylcarbamide;

(173) N-((4-Methylphenyl)methyl)-N-(1-(2-methylpropyl)piperidin-4-yl)-N′

-phenylmethylcarbamide;

(174) N-(1-((2-Bromophenyl)methyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-N′

-phenylmethylcarbamide;

(175) N-(4-Hydroxy-3-methoxyphenyl)methyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-N′

-phenylmethylcarbamide;

(176) N-(1-((5-Ethylthien-2-yOmethyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-N′

-phenylmethylcarbamide;

(177) N-(1-(Imidazol-2-ylmethyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-N′

-phenylmethylcarbamide;

(178) N-(1-(Cyclohexylmethyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-N′

-phenylmethylcarbamide;

(179) N-(1-((4-Fluorophenyl)methyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-N′

-phenylmethylcarbamide;

(180) N-((4-Methylphenyl)methyl)-N-(piperidin-4-yl)-4-methoxyphenylacetamide;

(181) N-((4-Methylphenyl)methyl)-N-(1-methylpiperidin-4-yl)-4-methoxyphenylacetamide;

(182) N-(1-Ethylpiperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;

(183) N-((4-Methylphenyl)methyl)-N-(1-propylpiperidin-4-yl)-4-methoxyphenylacetamide;

(184) N-(1-Butylpiperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;

(185) N-(1-(3,3-Dimethylbutyppiperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;

(186) N-(1-(Cyclohexylmethyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;

(187) N-((4-Methylphenyl)methyl)-N-(1-(2-methylpropyl)piperidin-4-yl)-4-methoxyphenylacetamide;

(188) N-((4-Methylphenyl)methyl)-N-(1-((4-methylphenyl)methyl)piperidin-4-yl)-4-methoxyphenylacetamide;

(189) N-(1-((4-Hydroxyphenyl)methyppiperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;

(190) N-(1-((2-Hydroxyphenyl)methyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;

(191) N-(3-Phenylpropyl)-N-(piperidin-4-yl)-4-methoxyphenylacetamide;

(192) N-(2-Phenylethyl)-N-(piperidin-4-yl)-4-methoxyphenylacetamide;

(193) N-((2-Methoxyphenyl)methyl)-N-(piperidin-4-yl)-4-methoxyphenylacetamide;

(194) N-((2-Chlorophenyl)methyl)-N-(piperidin-4-yl)-4-methoxyphenylacetamide;

(195) N-((3,4-Di-methoxyphenyl)methyl)-N-(piperidin-4-yl)-4-methoxyphenylacetamide;

(196) N-((4-Fluorophenyl)methyl)-N-(piperidin-4-yl)-4-methoxyphenylacetamide;

(197) N-((2,4-Di-chlorophenyl)methyl)-N-(piperidin-4-yl)-4-methoxyphenylacetamide;

(198) N-((3-Methylphenyl)methyl)-N-(piperidin-4-yl)-4-methoxyphenylacetamide;

(199) N-((3-Bromophenyl)methyl)-N-(piperidin-4-yl)-4-methoxyphenylacetamide;

(200) N-(1-(Phenylmethyl)piperidin-4-yl)-N-(3-phenyl-2-propen-1-yl)-4-methoxyphenylacetamide;

(201) N-((4-Methylphenyl)methyl)-N-(1-piperidin-4-yl)-phenylacetamide;

(202) N-((4-Methylphenyl)methyl)-N-(1-piperidin-4-yl)-3-phenylpropionamide;

(203) N-((4-Methylphenyl)methyl)-N-(1-piperidin-4-yl)-(phenylthio)acetamide;

(204) N-((4-Methylphenyl)methyl)-N-(1-piperidin-4-yl)-phenoxyacetamide;

(205) N-((4-Methylphenyl)methyl)-N-(1-piperidin-4-yl)-(4-chlorophenoxy)acetamide;

(206) N-((4-Methylphenyl)methyl)-N-(1-piperidin-4-yl)-3-methoxyphenylacetamide;

(207) N-((4-Methylphenyl)methyl)-N-(1-piperidin-4-yl)-4-fluorophenylacetamide;

(208) N-((4-Methylphenyl)methyl)-N-(1-piperidin-4-yl)-2,5-di-methoxyphenylacetamide;

(209) N-((4-Methylphenyl)methyl)-N-(1-piperidin-4-yl)-4-chlorophenylacetamide;

(210) N-((4-Methylphenyl)methyl)-N-(1-(phenylmethyl)pyrrolidin-3-yl)-N′

-phenylmethylcarbamide;

(211) N-((4-Methylphenyl)methyl)-N-(1-(phenylmethyl)pyrrolidin-3-yl)-4-methoxyphenylacetamide;

(212) 2-(4-methoxyphenyl)-N-((4-methylbenzyl)-N-(piperidin-4-yl)acetamide;

(213) 2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl)acetamide;

(214) 2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-(1-ethylpiperidin-4-yl)acetamide;

(215) 2-(4-methoxyphenyl)-N-(4-chlorbenzyl)-N-(1-ethylpiperidin-4-yl)acetamide;

(216) 2-(4-methoxyphenyl)-N-(4-chlorbenzyl)-N-(1-isopropylpiperidin-4-yl)acetamide;

(217) 2-(4-methoxyphenyl)-N-(4-chlorobenzyl)-N-(piperidin-4-yl)acetamide;

(218) 2-(4-methoxyphenyl)-N-(4-chlorobenzyl)-N-(1-cyclopentylpiperidin-4-yl)acetamide;

(219) 2-(4-methoxyphenyl)-N-(4-chlorbenzyl)-N-(1-isopropylpiperidin-4-yl)acetamide;

(220) 2-(phenyl)-N-(4-trifluoromethylbenzyl)-N-(1-methylpiperidin-4-yl)acetamide;

(221) 2-(4-fluorophenyl)-N-(4-trifluoromethylbenzyl)-N-(1-methylpiperidin-4-yl)acetamide;

(222) 2-(4-Methoxyphenyl)-N-(4-trifluoromethylbenzyl)-N-(1-methylpiperidin-4-yl)acetamide;

(223) 2-(4-Trifluoromethylphenyl)-N-(4-trifluoromethylbenzyl)-N-(1-methylpiperidin-4-yl)acetamide;

(224) 2-(4-Fluorophenyl)-N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)acetamide;

(225) 2-(4-Methoxyphenyl)-N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)acetamide;

(226) 2-(phenyl)-N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)acetamide;

(227) 2-(4-Trifluoromethylphenyl)-N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)acetamide;

(228) 2-(4-trifluoromethylphenyl)-N-[4-(methoxycarbonyl)benzyl]-N-(1-methylpiperidin-4-yl)acetamide;

(229) 2-Phenyl-N-[4-(methoxycarbonyl)benzyl]-N-(1-methylpiperidin-4-yl)acetamide;

(230) 2-(4-Chlorophenyl)-N-[4-(methoxycarbonyl)benzyl]-N-(1-methylpiperidin-4-yl)acetamide;

(231) 2-(4-Methoxyphenyl)-N-[4-(methoxycarbonyl)benzyl]-N-(1-methylpiperidin-4-yl)acetamide;

(232) 2-(4-trifluoromethylphenyl)-N-[4-(methoxycarbonyl)benzyl]-N-(1-methylpiperidin-4-yl)acetamide;

(233) 2-Phenyl-N-[4-(methoxycarbonyl)benzyl]-N-(1-methylpiperidin-4-yl)acetamide;

(234) 2-(4-Chlorophenyl)-N-[4-(methoxycarbonyl)benzyl]-N-(1-methylpiperidin-4-yl)acetamide;

(235) 2-(4-Methoxyphenyl)-N-[4-(methoxycarbonyl)benzyl]-N-(1-methylpiperidin-4-yl)acetamide;

(236) 2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-[1-(4-chloromethyl-2-thiazolylmethyl)piperidin-4-yl]acetamide, (237) 2-(4 methoxyphenyl)-N-(4-methylbenzyl)-N-{1-[3-(1,3-dihydro-2H-benzimidazol-2-on-1-yepropyl]piperidin-4-yl}acetamide;

(238) 2-(4-methoxyphenyl)-N-(2-4(fluorophenyl)ethyl)-N-(1-methylpiperidin-4-yl)acetamide;

(239) 2-(4-methoxyphenyl)-N-[2-(2,5-dimethoxyphenyl)ethyl]-N-(1-methylpiperidin-4-yl)acetamide;

(240) 2-(4-methoxyphenye-N-[2-(2,4-dichlorophenyl)ethyl]-N-(1-methylpiperidin-4-yl)acetamide;

(241) 2-(4-methoxyphenyl)-N-[2-(3-chlorophenyl)ethyl]-N-(1-methylpiperidin-4-yl)acetamide;

(242) 2-(4-methoxyphenyl)-N-[2-(4-methoxyphenyl)ethyl]-N-(1-methylpiperidin-4-yl)acetamide;

(243) 2-(4-methoxyphenyl)-N-[2-(3-fluorophenyl)ethyl]-N-(1-methylpiperidin-4-yl)acetamide;

(244) 2-(4-ethoxyphenyl)-N-[2-(4-fluorophenethyl]-N-(1-methylpiperidin-4-yl)acetamide;

(245) 2-(4-ethoxyphenyl)-N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)acetamide;

(246) 2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-{1-[2-(2-hydroxyethoxy)ethyl]piperidin-4-yl}acetamide;

(247) 2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-[1-((2-chloro-5-thienyl)methyl)piperidin-4-yl]acetamide;

(248) 2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-[1-(2-(imidazolidinon-1-yl)ethyl)piperidin-4-yl]acetamide;

(249) 2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-{1-[2-(2,4(1H,3H)quinazolinedion-3-yl)ethyl]piperidin-4-yl}acetamide;

(250) 2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-{1-[2-(1,3-dioxolan-2-yl)ethyl]piperidin-4-yl}acetamide;

(251) 2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-{1-[2-(3-indolyl)ethyl]piperidin-4-yl}acetamide;

(252) 2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-{1-[3-(1,2,4-triazol-1-yl)propyl]piperidin-4-yl}acetamide, (253) 2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-[1-(5-benzofurazanylmethyppiperidin-4-yl]acetamide;

(254) 2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-[1-(5-chlorobenzo[b]thien-3-ylmethyl)piperidin-4-yl]acetamide;

(255) 2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-[1-(5-phenyl-1,2,4-oxadiazol-3-ylmethyl)piperidin-4-yl]acetamide;

(256) 2-(4-Chlorophenyl)-N-(4-methylbenzyl)-N-(1-isopropylpiperidin-4-yl)-acetamide;

(257) 2-(4-Chlorophenyl)-N-(4-methylbenzyl)-N-(1-ethylpiperidin-4-yl)-acetamide;

(258) 2-Phenyl-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl)-acetamide;

(259) 2-(4-Chlorophenyl)-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl)-acetamide;

(260) 2-(4-Chlorophenyl)-N-(4-methylbenzyl)-N-(1-cyclopentylpiperidin-4-yl)-acetamide;

(261) 2-(4-Fluorophenyl)-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl)-acetamide;

(262) 2-(4-Chlorophenyl)-N-(4-methylbenzyl)-N-(1-(2-hydroxyethyl)-piperidin-4-yl)-acetamide;

(263) 2-(4-Chlorophenyl)-N-(4-methylbenzyl)-N-(1-cyclobutylpiperidin-4-yl)-acetamide;

(264) 2-(4-Methoxyphenyl)-N-(4-methylbenzyl)-N-(1-cyclobutylpiperidin-4-yl)-acetamide;

(265) 2-(4-Methoxyphenyl)-N-(4-methylbenzyl)-N-(tropin-4-yl)-acetamide;

(266) N-(4-Methylbenzyl)-N-(1-methylpiperidin-4-yl)-N′

-benzyl-carbamide;

(267) N-(4-Methylbenzyl)-N-(1-methylpiperidin-4-yl)-N′

-phenyl-carbamide;

(268) N-Phenethyl-N-(1-methylpiperidin-4-yl)-N′

-benzyl-carbamide;

(269) 2-Phenyl-N-(4-methoxybenzyl)-N-(1-methylpiperidin-4-yl)-acetamide;

(270) 2-(4-Trifluoromethylphenyl)-N-(4-methoxybenzyl)-N-(1-methylpiperidin-4-yl)-acetamide (271) 2-(4-Fluorophenyl)-N-(4-methoxybenzyl)-N-(1-methylpiperidin-4-yl)-acetamide;

(272) 2-(4-Methoxyphenyl)-N-(4-methoxybenzyl)-N-(1-methylpiperidin-4-yl)-acetamide;

(273) 2-(4-Methylphenyl)-N-(4-chlorobenzyl)-N-(1-methylpiperidin-4-yl)-acetamide;

(274) 2-(4-Hydroxyphenyl)-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl)-acetamide;

(275) N-Phenethyl-N-(1-methylpiperidin-4-yl)-N′

-phenyl-carbamide;

(276) N-(3-Phenylpropyl)-N-(1-methylpiperidin-4-yl)-N′

-benzyl-carbamide;

(277) N-(3-Phenylpropyl)-N-(1-methylpiperidin-4-yl)-N′

-phenyl-carbamide;

(278) 2-(4-Methoxyphenyl)-2,2-ethylene-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl)acetamide;

(279) 2-(4-Methoxyphenyl)-N-alpha-methylbenzyl-N-(1-methylpiperidin-4-yl)acetamide;

(280) 2-(4-Methoxyphenyl)-N-(4-methylbenzyl)-N-(3-tropen-4-yl)acetamide;

(281) 2-Phenyl-2-ethyl-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl)acetamide;

(282) N-Phenethyl-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl)-amine;

(283) 2-(4-Methoxyphenyl)-N-(1-indanyl)-N-(1-methylpiperidin-4-yl)acetamide;

(284) N-(4-Methylbenzyl)-N-(1-methylpiperidin-4-yl)-N′

-(4-methoxybenzyl)-carbamide;

(285) 2-(3,4-dimethoxyphenyl)-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl)acetamide;

(286) 2-(3,4-Methylenedioxyphenyl)-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl)acetamide;

(287) 2-(4-Methoxyphenyl)-N-(4-methylbenzyl)-N-(1-t-butylpiperidin-4-yl)-acetamide;

(288) N-(4-Methylbenzyl)-N-(1-methylpiperidin-4-yl)-N′

-phenethyl-carbamide;

(289) N-Phenethyl-N-(1-methylpiperidin-4-yl)-N′

-phenethyl-carbamide;

(290) N-(4-Methylbenzyl)-N-(1-t-butylpiperidin-4-yl)-N′

-(4-methoxybenzyl)-carbamide;

(291) 2-(4-Ethoxyphenyl)-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl)acetamide;

(292) 2-(4-Butoxyphenyl)-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl)acetamide;

(293) 2-(4-i-Propoxyphenyl)-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl)acetamide;

(294) 2-(4-t-Butoxyphenyl)-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl)acetamide;

(295) 2-(4-Butoxyphenyl)-N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)acetamide;

(296) 2-(4-Propoxyphenyl)-N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)acetamide;

(297) 2-(4-i-Propoxyphenyl)-N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)acetamide;

(298) 2-(4-t-Butoxyphenyl)-N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)acetamide;

(299) 4-(4-Fluorobenzyl)-3-(4-methoxybenzyl)-8-methyl-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(300) 3-(4-Ethoxybenzyl)-4-(4-fluorobenzyl)-8-methyl-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(301) 4-(4-Fluorobenzyl)-8-methyl-3-(4-propoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(302) 3-(4-Cyclopropylmethoxybenzyl)-4-(4-fluorobenzyl)-8-methyl-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(303) 4-(4-Fluorobenzyl)-3-(4-isopropoxybenzyl)-8-methyl-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(304) 3-(4-Butoxybenzyl)-4-(4-fluorobenzyl)-8-methyl-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(305) 4-(4-Fluorobenzyl)-3-(4-isobutoxybenzyl)-8-methyl-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(306) 3-(4-Difluoromethoxybenzyl)-4-(4-fluorobenzyl)-8-methyl-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(307) 4-(4-Fluorobenzyl)-8-methyl-3-(4-trifluoromethoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(308) 4-(4-Fluorobenzyl)-8-methyl-3-(4-pentoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(309) 8-Ethyl-4-(4-fluorobenzyl)-3-(4-isobutoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(310) 4-(4-Fluorobenzyl)-3-(4-isobutoxybenzyl)-8-isopropyl-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(311) 8-Cyclopropylmethyl-4-(4-fluorobenzyl)-3-(4-isobutoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(312) 8-Cyclohexylmethyl-4-(4-fluorobenzyl)-3-(4-isobutoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(313) 8-Cyclopentyl-4-(4-fluorobenzyl)-3-(4-isobutoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(314) 4-(4-Fluorobenzyl)-3-(4-isobutoxybenzyl)-8-(3-morpholin-4-yl-propyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(315) 8-(2-[1,3]Dioxolan-2-yl-ethyl)-4-(4-fluorobenzyl)-3-(4-isobutoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(316) 4-(4-Fluorobenzyl)-3-(4-isobutoxybenzyl)-8-[2-(2-oxo-imidazolidin-1-yl)-ethyl]-1-oxa-3,8-diaza-spiro[4.5]decan-2-one, (317) 4-(4-Fluorobenzyl)-3-(4-isobutoxybenzyl)-8-[3-(2-oxo-2,3-dihydro-benzoimid azol-1-yl)-propyl]-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(318) 4-(4-Fluorobenzyl)-3-(4-isobutoxybenzyl)-8-(2-methyl-thiazol-4-yl-methyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(319) 4-(4-Chlorobenzyl)-3-(4-isobutoxybenzyl)-8-methyl-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(320) 8-Ethyl-4-(4-chlorobenzyl)-3-(4-isobutoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(321) 4-(4-Chlorobenzyl)-3-(4-isobutoxybenzyl)-8-isopropyl-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(322) 8-Cyclopropylmethyl-4-(4-chlorobenzyl)-3-(4-isobutoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(323) 8-Cyclohexylmethyl-4-(4-chlorobenzyl)-3-(4-isobutoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(324) 8-(2-[1,3]Dioxolan-2-yl-ethyl)-4-(4-chlorobenzyl)-3-(4-isobutoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(325) 4-(4-Chlorobenzyl)-3-(4-isobutoxybenzyl)-8-[2-(2-oxo-imidazolidin-1-yl)-ethyl]-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(326) 3-(4-Difluoromethoxybenzyl)-4-(4-fluorobenzyl)-8-methyl-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(327) 3-(4-Difluoromethoxybenzyl)-8-ethyl-4-(4-fluorobenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(328) 3-(4-Difluoromethoxybenzyl)-4-(4-fluorobenzyl)-8-isopropyl-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(329) 8-Cyclopropylmethyl-3-(4-difluoromethoxybenzyl)-4-(4-fluorobenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(330) 8-Cyclohexylmethyl-3-(4-difluoromethoxybenzyl)-4-(4-fluorobenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(331) 3-(4-Difluoromethoxybenzyl)-8-(2-[1,3]dioxolan-2-yl-ethyl)-4-(4-fluorobenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(332) 3-(4-Difluoromethoxybenzyl)-4-(4-fluorobenzyl)-8-[2-(2-oxo-imidazolidin-1-yl)-ethyl]-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(333) 8-Ethyl-4-(4-fluorobenzyl)-3-(4-trifluoromethoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(334) 4-(4-Fluorobenzyl)-8-isopropyl-3-(4-trifluoromethoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(335) 8-Cyclopropylmethyl-4-(4-fluorobenzyl)-3-(4-trifluoromethoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(336) 8-Cyclohexylmethyl-4-(4-fluorobenzyl)-3-(4-trifluoromethoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(337) 8-Cyclopentyl-4-(4-fluorobenzyl)-3-(4-trifluoromethoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(338) 8-(2-[1,3]Dioxolan-2-yl-ethyl)-4-(4-fluorobenzyl)-3-(4-trifluoromethoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(339) 4-(4-Fluorobenzyl)-8-[2-(2-oxo-imidazolidin-1-yl)-ethyl]-3-(4-trifluoromethoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(340) 8-Ethyl-4-(4-fluorobenzyl)-3-(4-propoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(341) 4-(4-Fluorobenzyl)-8-isopropyl-3-(4-propoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(342) 8-Cyclopropylmethyl-4-(4-fluorobenzyl)-3-(4-propoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(343) 8-Cyclohexylmethyl-4-(4-fluorobenzyl)-3-(4-propoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(344) 8-Cyclopentyl-4-(4-fluorobenzyl)-3-(4-propoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(345) 8-(2-[1,3]Dioxolan-2-yl-ethyl)-4-(4-fluorobenzyl)-3-(4-propoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(346) 4-(4-Fluorobenzyl)-8-[2-(2-oxo-imidazolidin-1-yl)-ethyl]-3-(4-propoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(347) 3-(4-Cyclopropylmethoxybenzyl)-8-ethyl-4-(4-fluorobenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(348) 3-(4-Cyclopropylmethoxybenzyl)-4-(4-fluorobenzyl)-8-isopropyl-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(349) 3-(4-Cyclopropylmethoxybenzyl)-8-cyclopropylmethyl-4-(4-fluorobenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(350) 3-(4-Cyclopropylmethoxybenzyl)-8-(2-[1,3]dioxolan-2-yl-ethyl)-4-(4-fluorobenzyl)-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(351) 3-(4-Cyclopropylmethoxybenzyl)-4-(4-fluorobenzyl)-8-[2-(2-oxo-imidazolidin-1-yl)-ethyl]-1-oxa-3,8-diaza-spiro[4.5]decan-2-one;

(352) 8-(2-[1.3]-Dioxan-2-yl-ethyl)-4-(4-fluorobenzyl)-3-(4-isobutoxybenzyl)-1-oxa-3,8-diaza-spiro[4.5]decane-3-one;

(353) 4-(4-Fluorobenzyl)-3-(4-isobutoxybenzyl)-8-{3-[(S)-4-isopropyl-2-oxo-oxazolidin-3-yl]-propyl}spiro[4.5]decane-3-one;

(354) N-{1-[2-(1,3-Dioxolan-2-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-N′

-(4-isobutoxybenzyl)carbamide hydrochloride;

(355) N-{1-[2-(1,3-Dioxan-2-yl)ethyl]-piperidin-4-yl}-N-(4-fluorobenzyl)-2-[4-(2-hydroxy-2-methylpropoxy)phenyl]-acetamide tartrate;

(356) N-(4-Fluorobenyzl)-N-(piperidin-4-yl)-2-(4-isobutoxyphenyl)acetamide;

(357) N-{1-[3-(3,5-Dimethylpiperidin-1-yl)propyl]piperidin-4-yl-}-N-(4-fluorobenzyl)-2-(4-isobutoxyphenyl)acetamide dihydrochloride;

(358) 1-[3-(4-{(4-Fluorobenzyl)-[2-(4 isobutoxyphenyl)acetyl]amino}piperidin-1-yl)propyl]piperidine-4-carboxylic acid methyl ester dihydrochloride;

(359) N-(4-Fluorobenzyl)-2-(4-isobutoxyphenyl)-N-{1-[2-(1-methylpyrrolidin-2-yl-)ethyl]piperidin-4-yl}acetamide dioxalate;

(360) N-{1-[3-(2,6-Dimethylmorpholin-4-yl)propyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-(44 sobutoxyphenyl)acetamide dioxalate;

(361) N-(4-Fluorobenzyl)-N-{1-[3-(3-hydroxypiperidin-1-yl)propyl]piperidin-4-yl}-2-(4-isobutoxyphenyl)acetamide dioxalate;

(362) N-(4-Fluorobenzyl)-2-(4-isobutoxyphenyl)-N-{1-[3-(2-methylpiperidin-1-yl)-propyl]piperidin-4-yl}acetamide dioxalate;

(363) N-(4-Fluorobenzyl-2-(4-isobutoxyphenyl)-N-[1-(3-pyrrolidin-1-yl-propyl)piperidin-4-yl]acetamide dioxalate;

(364) N-{1-[3-(2,5-Dimethylpyrroli din-1-yl)propyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-isobutoxyphenyl)acetamide dioxalate;

(365) N-(4-Fluorobenzyl)-N-{1-[3-(3-hydroxymethylpiperidin-1-yl)propyl]piperidin-4-yl}-2-(4-isobutoxyphenyl)acetamide dioxalate;

(366) N-(4-Fluorobenzyl)-2-(4-isobutoxyphenyl)-N-{1-[3-(4-(S)-isopropyl-2-oxo-oxazolidin-3-yl)propyl]piperidin-4-yl}acetamide oxalate;

(367) N-[2-(4-Fluorophenyl)ethyl]-2-(4-isobutoxyphenyl)-N-{1-[3-(4-(S)-isopropyl-2-oxo-oxazolidin-3-yl)propyl]piperidin-4-yl}acetamide oxalate;

(368) N-[2-(4-Fluorophenyl)ethyl]-N-{1-[3-(4-(S)-isopropyl-2-oxo-oxazolidin-3-yl)propyl]piperidin-4-yl}-2-(4-propoxyphenyl)acetamide oxalate;

(369) N-(4-Fluorobenzyl)-N-{1-[3-(4-(S)-isopropyl-2-oxo-oxazolidin-3-yl)propyl]piperidin-4-yl}-2-(4-propoxyphenyl)acetamide oxalate;

(370) N-{1-[2-(1,3-Dioxan-2-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-isobutoxyphenyl)acetamide oxalate;

(371) N-{1-[2-(1,3-Dioxan-2-yl)ethyl]piperidin-4-yl}-N-[2-(4-fluorophenyl)ethyl]-2-(4-isobutoxyphenyl)acetamide oxalate;

(372) N-{1-[2-(1,3-Dioxan-2-yl)ethyl]piperidin-4-yl}-N-[2-(4-fluorophenyl)ethyl]-2-(4-propoxyphenyl)acetamide oxalate;

(373) N-{1-[2-(1,3-Dioxan-2-yl-)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-propoxyphenyl)acetami de tartrate;

(374) N-{1-[2-(1,3-Dioxan-2-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-N′

-(4-isobutoxybenzyl)carbami de tartrate;

(375) N-{1-[2-(1,3-Dioxan-2-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-fluorophenyl)acetamide tartrate;

(376) N-{1-[2-(1,3-Dioxan-2-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-p-tolylacetamide tartrate;

(377) 2-Benzofuran-5-yl-N-{1-[2-(1,3-dioxan-2-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)acetamide tartrate;

(378) 2-(2,3-Dihydrobenzofuran-5-yl)-N-{1-[2-(1,3-dioxan-2-yDethyl]piperidin-4-yl}-N-(4-fluorobenzyl)acetamide tartrate;

(379) N-{1-[2-(2,2-Dimethyl-1,3-dioxolan-4-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-isobutoxyphenyl)acetamide tartrate;

(380) N-{1-[2-(1,3-Dioxan-4-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)amine;

(381) N-{1-[2-(1,3-Dioxan-4-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-isobutoxyphenyl)acetamide tartrate;

(382) N-{1-[2-(1,3-Dioxan-4-yl)ethyl]piperidin-4-yl}-N(4-fluorobenzyl)-2-(4-trifluoromethylphenyl)acetamide tartrate;

(383) 2-(4-Cyanophenyl)-N-{1-[2-(1,3-dioxan-4-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)acetamide tartrate;

(384) N-(4-Fluorobenzyl)-2-(4-isobutoxyphenyl)-N-{1-[2-(2-oxo-imidazolidin-1-yl)ethyl]piperidin-4-yl}acetamide hydrochloride;

(385) 2-(4-Methoxyphenyl)-N-(4-methylbenzyl)-N-{1-[2-(2-oxo-imidazolidin-1-yl)ethyl]piperidin-4-yl}acetamide hydrochloride;

(386) N-(4-Fluorobenzyl)-2-(4-isopropoxyphenyl)-N-{1-[2-(2-oxo-imidazolidin-1-yl)ethyl]piperidin-4-yl}acetamide hydrochloride;

(387) N-(4-Fluorobenzyl)-2-(4-isopropoxyphenyl)-N-{1-[3-(3-methyl-2-oxo-2,3-dihydro-benzoimidazol-1-yl)propyl]piperidin-4-yl}acetamide hydrochloride;

(388) N-{1-[2-(2,4-Dioxo-1,4-dihydro-2H-quinazolin-3-yl)ethyl]piperidin-4-yl}-2-(4-methoxyphenyl)-N-(4-methylbenzyl)acetamide hydrochloride;

(389) 2-(4-Methoxyphenyl)-N-(4-methylbenzyl)-N-{1-[3-(2-oxo-2,3-dihydrobenzoimidazol-1-yl)propyl]piperidin-4-yl}-acetamide hydrochloride;

(390) N-(4-Fluorobenzyl)-2-(4-isopropoxyphenyl)-N-{1-[4-(2-oxo-2,3-dihydrobenzoimidazol-1-yl)butyl]piperidin-4-yl}acetamide hydrochloride;

(391) N-{1-[2-(2,4-Dioxo-1,4-dihydro-2H-quinazolin-3-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-isopropoxyphenyl)acetamide hydrochloride;

(392) 4-(4-Fluorobenzylamino)-piperidine-1-carboxylic acid benzyl ester;

(393) N-(1-Benzyloxycarbonylpiperidin-4-yl)-N-(4-fluorobenzyl)-N′

-(4-isopropoxybenzyl)carbamide;

(394) N-(4-Fluorobenzyl)-N′

-(4-isopropoxybenzyl)-N-piperidin-4-yl-carbamide oxalate;

(395) N-{1-[2-(1,3-Dioxolan-2-yl)ethyl}piperidin-4-yl]-N-(4-fluorobenzyl)-N′

-(4-isopropoxy-benzyl)carbamide oxalate;

methoxyphenyl)-N-(4-methylbenzyl)acetamide hydrochloride;

(397) N-{1-[2-(1,3-Dioxolan-2-yl-)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-isobutoxyphenyl)acetamide hydrochloride;

(398) N-{1-[2(1,3-Dioxolan-2-yl)ethyl]piperidin-4-yl}-2-(4-isopropoxyphenyl)-N-(4-methylbenzyl)acetamide hydrochloride;

(399) N-{1-[2-(1,3-Dioxolan-2-yeethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-propoxyphenyl)acetamide tartrate;

(400) N-(4-Fluorobenzyl)-N′

-(4-isopropoxybenzyl)-N-{1-[2-((S)-4-methyl-1,3-dioxolane-2-yl)ethyl]piperidin-4-yl}-carbamide oxalate;

(401) N-(4-Fluorobenzyl)-N′

-(4-isopropoxybenzyl)-N-[1-(3-morpholin-4-yl-propyl)piperidin-4-yl]carbamide oxalate;

(402) 2-(4-Methoxyphenye-N-(4-methylbenzyl)-N-[1-(2-morpholin-4-yl-ethyppiperidin-4-yl]acetamide dihydrochloride;

(403) 2-(4-Methoxyphenyl)-N-(4-methylbenzyl)-N-[1-(3-morpholin-4-ylpropyl)piperidin-4-yl]acetamide dihydrochloride;

(404) N-(4-Fluorobenzyl)-2-(4-isobutoxyphenyl)-N-[1-(3-morpholin-4-ylpropyl)piperidin-4-yl]acetamide dihydrochloride;

(405) N-(4-Fluorobenzyl)-2-(4-isopropoxy-phenyl)-N-[1-(3-morpholin-4-yl-propyl)piperidin-4-yl]acetamide dihydrochloride;

(406) N-(4-Fluorobenzyl)-N′

-(4-isopropoxybenzyl)-N-[1-(3-piperidin-1-yl-propyl)piperidin-4-yl]carbamide oxalate;

(407) N-(4-Fluorobenzyl)-N′

-(4-isopropoxybenzyl)-N-[1-(3-((S)-4-isopropyl-2-oxazolidinon-1-yl-propyl)piperidin-4-yl]carbamide tartrate;

(408) N-(4-Fluorobenzyl)-N′

-(4-isopropoxybenzyl)-N-{1-[2-(2,5,5-trimethyl-1,3-dioxan-2-yl)ethyl]lpiperidin-4-yl}carbamide oxalate;

(409) N-{1-[3-(1,3-Dioxolan-2-yl)propyl]piperidin-4-yl}-N-(4-fluorobenzyl)-N′

-(4-isopropoxybenzyl)carbamide oxalate;

(410) N-[1-(2,2-Dimethyl-1,3-dioxan-5-yl)-piperidin-4-yl]-N-(4-fluorobenzyl)-N′

-(4-isopropoxybenzyl)carbamide oxalate;

(411) N-(4-Fluorobenzyl)-N′

-(4-isopropoxybenzyl)-N-{[2-(1-methylpyrrolidin-2-yl)ethyl]-piperidin-4-yl}carbamide oxalate;

(412) N-[1-(2,2-Dimethyl-1,3-dioxan-5-yl)piperidin-4-yl]-N-(4-fluorobenzyl)-2-(4-isobutoxyphenyl)acetamide oxalate;

(413) N-[1-(1,3-Dioxan-5-yl)-piperidin-4-yl)-N-(4-fluorobenzyl)-2-(4-isobutoxyphenyl)acetamide tartrate;

(414) N-[1-(2,2-Dimethyl-1,3-dioxan-5-yl)piperidin-4-yl]-N-(4-fluorobenzyl)-2-(4-fluorophenyl)acetamide tartrate;

(415) N-{1-[2-(1,3-Dioxan-4-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-fluorophenyl)acetamide tartrate;

(416) N-{1-[2-(1,3-Dioxan-4-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-trifluoromethoxyphenyl)acetamide tartrate;

(417) N-{1-[2-(1,3-Dioxan-4-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-propoxyphenyl)acetamide tartrate;

(418) N-(4-Fluorobenzyl)-2-(4-isobutoxyphenyl)-N-[1-(tetrahydropyran-4-yppiperidin-4-yl]acetamide tartrate;

(419) N-(4-Fluorobenzyl)-2-(4-isobutoxyphenyl)-N-[1-(tetrahydropyran-4-ylmethyl)piperidin-4-yl]acetamide tartrate;

(420) N-(4-Fluorobenzyl)-2-(4-isobutoxyphenyl)-N-{1-[2-(tetrahydropyran-4-yl)ethyl]piperidin-4-yl]acetamide tartrate;

(421) N-(4-Fluorobenzyl)-2-(4-fluorophenyl)-N-[1-(tetrahydropyran-4-yl)piperidin-4-yl]acetamide tartrate;

(422) N-[14(S)-3,5-Dihydroxypentyppiperidine-4-yl]-N-(4-fluorobenzyl)-2-(4-isobutoxyphenyl)acetamide tartrate;

(423) N-{1-[2-((4S)-1,3-Dioxane-4-yl)ethyl]piperidine-4-yl}-N-(4-fluorobenzyl)-2(4-isobutoxyphenyl)acetamide tartrate;

(424) N-{1-[2-(1,3-Dioxan-2-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)amine;

(425) 2-(4-Benzyloxyphenyl)-N-{1-[2-(1,3-dioxan-2-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)acetamide tartrate;

(426) N-{1-[2-(1,3-Dioxan-2-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-hydroxyphenyl)-acetamide tartrate;

(427) N-{1-[2-(1,3-Dioxan-2-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-methoxyphenyl)-acetamide tartrate;

(428) N-{1-[2-(1,3-Dioxan-2-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-isopropylphenyl)-acetamide tartrate;

(429) N-{1-[2-(1,3-Dioxan-2-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-trifluoromethoxy-phenyl)acetamide tartrate;

(430) N-{1-[2-(1,3-Dioxan-2-yl)ethyl]-piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-ethoxyphenyl)-acetamide oxalate;

(431) N-{1-[2-(1,3-Dioxan-2-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-isopropoxyphenyl)-acetamide oxalate;

(432) N-{1-[2-(1,3-Dioxan-2-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-phenylacetamide oxalate;

(433) N-{1-[2-(1,3-Dioxan-2-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-[4-(2-fluoroethoxy)-phenyl]acetamide oxalate;

(434) N-{1-[2-(5,5-Dimethyl-1,3-dioxan-2-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-isobutoxyphenyl)acetamide oxalate;

(435) N-(4-Fluorobenzyl)-2-(4-isobutoxyphenyl)-N-{1-[2-((R)-4-methyl-1,3-dioxan-2-yl)ethyl]-piperidin-4-yl}acetamide oxalate;

(436) N-(4-Fluorobenzyl)-2-(4-isobutoxyphenyl)-N-{1-[2-((S)-4-methyl-1,3-dioxolan-2-yl)ethyl]piperidin-4-yl}acetamide oxalate;

(437) N-{1-[2-(4,6-Dimethyl-1,3-dioxan-2-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-isobutoxyphenyl)acetamide oxalate;

(438) N-(4-Fluorobenzyl)-N-{1-[2-((S)-4-methyl-1,3-dioxolan-2-yl)ethyl]piperidin-4-yl}-2-(4-trifluoromethoxyphenyl)acetamide oxalate;

(439) N-(4-Fluorobenzyl)-2-(4-isopropylphenyl)-N-{1-[2-((S)-4-methyl-1,3-dioxolan-2-yl)ethyl]-piperidin-4-yl}acetamide oxalate;

(440) N-(4-Fluorobenzyl)-N-{1-[2-((R)-4-methyl-1,3-dioxan-2-yl)ethyl]piperidin-4-yl}-2-(4-trifluoromethoxyphenyl)acetamide oxalate;

(441) N-(4-Fluorobenzyl)-2-(4-isobutoxyphenyl)-N-{1-[2-(2,5,5-trimethyl-1,3-dioxan-2-yl)ethyl]piperidin-4-yl}acetamide oxalate;

(442) N-(4-Fluorobenzyl)-2-(4-isobutoxyphenyl)-N-{1-[2-(2-methyl-1,3-dioxolan-2-yl)ethyl]-piperidin-4-yl-}acetamide oxalate;

(443) N-(4-Fluorobenzyl)-2-(4-isobutoxyphenyl)-N-{1-[3-(1,3-dioxolan-2-yl)propyl]piperidin-4-yl}acetamide tartrate;

(444) N-(4-Fluorobenzyl)-2-(4-isobutoxyphenyl)-N-{1-(3-piperidin-1-yl-propyl)piperidin-4-yl}-acetamide dihydrochloride;

(445) N-(4-Fluorobenzyl)-2-(4-isobutoxyphenyl)-N-{1-[2-(tetrahydropyran-2-yloxy)ethyl]-piperidin-4-yl}acetamide oxalate;

(446) N-(4-Fluorobenzyl)-2-(4-isobutoxyphenyl)-N-{1-[3-(2-oxo-piperidin-1-yepropyl]piperidin-4-yl}acetamide;

(447) N-(4-Fluorobenzyl)-2-(4-isobutoxyphenyl)-N-{1-[3-(2-oxo-pyrrolidin-1-yl)propyl]piperidin-4-yl}acetamide hydrochloride;

(448) N-(4-Fluorobenzyl)-2-(4-isobutoxyphenyl)-N-{1-[3-((R)-4-isopropyl-2-oxo-oxazolidin-3-yepropyl]piperidin-4-yl}acetamide oxalate;

(449) N-(4-Fluorobenzyl)-2-(4-isobutoxyphenyl)-N-{1-[3-(2-oxo-oxazolidin-3-yl)propyl]piperidin-4-yl}acetamide oxalate;

(450) N-(4-Fluorobenzyl)-2-(4-isobutoxyphenyl)-N-{1-[3-((S)-4-methyl 2-oxo-oxazolidin-3-yl)propyl]piperidin-4-yl}acetamide tartrate;

(451) N-(4-Fluorobenzyl)-2-(4 isobutoxyphenyl)-N-{1-[3-((S)-4-ethyl-2-oxo-oxazolidin-3-yl)-propyl]piperidin-4-yl}acetamide oxalate;

(452) N-(4-Fluorobenzyl)-2-(4-isobutoxyphenyl)-N-{1-[2-(1,3-oxothiolan-2-yl)ethyl]piperidin-4-yl}acetamide L-tartrate;

(453) 2-(4-Bromophenyl)-N-{1-[2-(1,3-dioxan-2-yl)ethyl)piperidin-4-yl}-N-(4-fluorobenzyl)-acetamide L-tartrate;

(454) N-{1-[2-(1,3-Dioxan-2-yl)ethyl)piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-isobutylamino-phenyl)acetamide L-tartrate;

(455) N-{1-[2-(1,3-Dioxan-2-yl)ethyl)piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-propylaminophenyl)acetamide L-tartrate;

(456) N-{1-[2-(1,3-Dioxan-2-yl)ethyl)piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-(1-nitropropyl)-phenyl)acetamide L-tartrate;

(457) N-{1-[2 (1,3-Dioxan-2-yl)ethyl)piperidin-4-yl}-N-(4-fluorobenzyl)-2-[4-(2-oxopyrrolidin-1-yl)phenyl)acetamide L-tartrate;

(458) N-{1-[2-(1,3-Dioxan-2-yl)ethyl)piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-isobutylsulfanylphenyl)acetamide L-tartrate;

(459) N-{1-[2-(1,3-Dioxan-2-yl)ethyl)piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-iodophenyl)-acetamide L-tartrate;

(460) 2-(4-Acetophenyl)-N-{1-[2-(1,3-dioxan-2-yl)ethyl)piperidin-4-yl}-N-(4-fluorobenzyl)-acetamide L-tartrate;

(461) 2-[4-(1-hydroxyiminoethyl)phenyl]-N-{1-[2-(1,3-dioxan-2-yl)ethyl)piperidin-4-yl}-N-(4-fluorobenzyl)acetamide L-tartrate;

(462) N-{1-[2-(1,3-Dioxan-2-yl)ethyl)piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-morpholin-4-yl-phenyl)acetamide L-tartrate;

(463) N-{1-[2-(1,3-Dioxan-2-yl)ethyl)-piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-pyrazol-1-ylphenyl)acetamide L-tartrate;

(464) N-{1-[2-(1,3-Dioxan-2-yl)-1-methylethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-isobutoxyphenyl)-acetamide L-tartrate;

(465) N-{1-[2-(1,3-Dioxan-4-yl)ethyl)piperidin-4-yl}-N-(4-fluorobenzyl)-2-(4-pyrazol-1-ylphenyl)acetamide L-tartrate;

(466) N-[1-((R)-3,5-Dihydroxypentyl)piperidine-4-yl]-N-(4-fluorobenzyl)-2-(4-isobutoxyphenyl)acetamide tartrate;

(467) N-{1-[2-((4R)-1,3-Dioxane-4-yl)ethyl]piperidine-4-yl}-N-(4-fluorobenzyl)-2-(4-isobutoxyphenyeacetamide tartrate;

(468) N-{1-[2-(1,3-Dioxan-2-yl)ethyl]piperidin-4-yl}-N-(4-fluorobenzyl)-2-[4-(1,2,4-triazol-4-yl)phenyl]acetamide L-tartrate;

(469) nortriptyline;

(470) duloxetine;

(471) lofepramine;

(472) tomoxetine;

(473) 3-({1-[2-(7-methyl-5-oxo-5H)-[1,3]thiazolo[3,2-a]pyrimidin-6-yl)ethyl]-3-pyrrolidinyl}methyl)-1H-indole-5-carbonitrile hydrochloride;

(474) 3-({1-[2-(6-chloro-2-oxo-2,3-dihydro-1H-indol-5-yl)ethyl]-3-pyrrolidinyl}-methyl)-1H-indole-5-carbonitrile hydrochloride;

(475) moclobemide;

(476) N-acetylserotonin;

(477) bromfaromine;

(478) beflaxozone;

(479) chlorimipramine;

(480) cyanimipramine;

(481) cianopramine;

(482) desipramine;

(483) protriptyline;

(484) trimipramine;

(485) doxepin;

(486) cyclobenzaprine;

(487) 5-methoxycarbonylamino-N-acetyltryptamine;

(488) amoxapine;

(489) maprotiline;

(490) fefazodone;

(491) flesinoxan hydrochloride;

(492) urapidil;

(493) WY47846 (3a,4,4a,6a,7,7a-hexahydro-2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]-butyl]-4,7-etheno-1H-cyclobutano[f]isoindole-1,3(2H)-dione dihydrochloride sesquihydrate);

(494) SM3997 (N-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-bicyclo[2.2.1]heptane-2,3-di-exo-carboximide);

(495) 2-(4-(4-(2-pyrimidinyl)-1-piperazinyl-propyl)-1,2-benzoisothiazol-3-(2H)-one 1,1-dioxide hydrochloride;

(496) KC9172 (3-butyl-9,9-dimethyl-7-[4-[4-[2-methoxyphenyl)-1-piperazinyl]butyl]-3,7-diazabicyclo[3,2,1]nonane-2,4,6,8-tetraone);

(497) 4-(N,N-dipropylamino)-6-methoxy-1,3,4,5-tetrahydrobenz-[c,d]indole;

(498) 4-[4-(N-1,2-benzisothiazol-3(2H)-one 1,1-dioxido)]butylamino-6-methoxy-1,3,4,5-tetrahydrobenz[c,d]-indole hydrochloride;

(499) 5-carboxamidotryptamine;

(500) N,N-dipropyl-5-carboxamidotryptamine;

(501) AH25086 (3-(2-aminoethyl)-1H-indole-5-(N-methyl)acetamide);

(502) GR43175 (3-(2-dimethylaminoethyl)-1H-indole-5-(N-methyl)methanesulfonamide);

(503) 3-(2-[4-[2-(1,2-benzisothiazole-3(2H)-one 1,1-dioxido)]butyl]amino)ethyl-5-methoxy-1H-indole;

(504) spiroxatrine;

(505) MDL72832 (8-[4-(1,4-benzodioxan-2-ylmethylamino)butyl]-8-azaspiro-[4,5]decane-7,9-dione);

(506) 2-[4-(1,4-benzodioxan-2-ylmethylamino)butyl]-1,2-benzisothiazol-3(2H)-one 1,1-dioxide;

(507) 2-(N,N-dipropylamino)-8-hydroxy-1,2,3,4-tetrahydronaphthalene;

(508) 2-{4-[2-(1,2-benzisothiazol-3(2H)-one 1,1-dioxido)]butyl}amino-8-methoxy-1,2,3,4-tetrahydronaphthalene;

(509) 3-N,N-dipropylamino-5-hydroxy-thiochroman;

3-N,N-dipropylamino-5-ethoxy-thiochroman;

(510) 3-N,N-dipropylamino-5-ethoxychroman;

(511) 1-[2-(3-indolyl)]-ethyl-2,6-dimethyl-piperidine;

(512) 1-{2-[3-(5-carboxamido)indolyl]}ethyl-2,6-dimethylpiperidine;

(513) RU24924 (5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl]-1H-indole);

(514) 5-methoxy-3-(1,2,3,6-tetrahydropyridin-5-yl)-1H-indole;

(515) diethyl N-benzyloxycarbonyl-5-benzyloxycarbonyloxy-L-tryptophyl-L-aspartate;

(516) dibenzyl N-benzyloxycarbonyl-5-hydroxy-L-tryptophanylaspartate;

(517) 5-Hydroxy-L-tryptophyl-L-aspartic acid trihydrate;

(518) diethyl N-benzyloxycarbonyl-5-hydroxy-L-tryptophyl-L-glutamate;

(519) diethyl 5-hydroxy-L-tryptophyl-L-glutamate hydrochloride;

(520) dibenzyl L-benzyloxycarbonyl-5-hydroxytryptophyl-L-glutamate;

(521) 5-hydroxy-L-tryptophyl-L-glutamic acid;

(522) pentachlorophenyl ester of N-benzyloxycarbonyl-5-hydroxy-L-tryptophan;

(523) methyl ester of N-benzyloxycarbonyl-5-hydroxy-L-tryptophyl-L-tyrosine;

(524) N-Acetyl-5-hydroxy-L-tryptophan;

(525) methyl ester of N-acetyl-5-hydroxy-L-tryptophyl-L-tyrosine;

(526) methyl ester of N-acetyl-5-hydroxy-L-tryptophyl-5-hydroxy-L-tryptophan;

(527) 5-hydroxy-L-tryptophyl-L-alanine hydrate;

(528) 5-hydroxy-L-tryptophan-L-valine;

(529) 5-hydroxy-L-tryptophyl-L-leucine;

(530) 5-hydroxy-L-tryptophyl-L-proline;

(531) 5-hydroxy-L-tryptophyl-L-phenylalanine;

(532) 5-hydroxy-L-tryptophyl-5-hydroxy-L-tryptophan;

(533) 5-hydroxy-L-tryptophyl-L-tryptophan;

(534) 1-(5-hydroxy)tryptophyl-L-serine;

(535) 5-hydroxy-L-tryptophyl-L-arginine;

(536) 5-hydroxy-L-tryptophylglycine;

(537) 5-hydroxy-1-tryptophyl-gamma-aminobutyric acid;

(538) 5-hydroxy-L-tryptophanamide hydrate;

(539) methyl ester of 5-hydroxy-L-tryptophyl-L-histidine;

(540) benzyl ester of L-5-hydroxytryptophan;

(541) benzyl ester of N-benzyloxycarbonyl-5-hydroxy-L-tryptophyl-5-hydroxy-L-tryptophan;

(542) 5-Hydroxy-L-tryptophyl-5-hydroxy-L-tryptophan hemihydrate;

(543) 5-hydroxytryptophan inosinate;

(544) theophylline salt of (DL) 5-hydroxytryptophan;

(545) RU25591 (6,7,8,9-tetrahydro N,N-dimethyl 5-[4-nitrophenyl]oxy 5H-benzocyclohepten 7-amine) cis-fumarate);

(546) LM5008 (4-[2-(3-indolyl)ethyl]piperidine);

(547) DU24565 (6-nitro-2-(1-piperazinyl)quinoline);

(548) CGP6085/A (4-(5,6-dimethyl-2-benzofuranyl)piperidine hydrochloride);

(549) alaprociate;

(550) dibenzoxazepine;

(551) deprenyl;

(552) isocarboxazide;

(553) furazolidone;

(554) procarbazine;

(555) Ro 60-0175/ORG 35030 ((S)-2-(4,4,7-trimethyl-1,4-dihydro-indeno (1,2-B) pyrrol-1-yl)-1-methyl-ethylamine) (556) Ro 60-0332/ORG 35035 ((S)-2-(Chloro-5-fluoro-indol-1-yl)-1-methylethylamine);

(557) 1-[6-Chloro-5-trifluoromethyl)-2-pyridinyl]-piperazine hydrochloride;

(558) 5-carboxyamidotryptamine;

(559) SB 206553 (3,5-Dihydro-5-methyl-N-3-pyridinylbenzo[1,2-b;

4,5-H]dipyrrole-1(2H)-carboxamide hydrochloride);

(560) ondansetron;

(561) granisetron;

(562) tropisetron;

(563) dolasetron;

(564) palonosetron;

(565) trimethobenzamide;

(566) risperidone;

(567) clozapine;

(568) azatadine;

(569) cyproheptadine;

(570) fenclonine;

(571) chlorpromazine;

(572) (3β

)-2,3-dihydrolysergine;

(573) (30)-2,3-dihydroisolysergine, (574) (3β

, 5β

, 8β

)-9,10-didehydro-2,3-dihydro-6-methylergoline-8-acetonitrile;

(575) 251-NBMD (2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2,3-methylenedioxyphenyl)methyl]ethanamine);

(576) N-(2-methoxybenzyl)-1-(8-bromo-2,3,6,7-tetrahydrobenzo[1,2-b;

4,5-b′

]difuran-4-yl)-2-aminoethane;

(577) 5-benzyloxytryptamine;

(578) 5-methoxy-7-N,N-dimethyltryptamine;

(579) A372159 ((11S,16R)-3-[4-(propan-2-yloxy)-2-(trifluoromethyl)phenyl]-6-oxa-10,14-diazatetracyclo[8.6.1.0^5,17.0^11,16]heptadeca-1,3,5(17)-triene);

(580) AL-34662 (14(S)-2-Aminopropyl)-1H-indazol-6-ol);

(581) AL-37350A ((S)-(+)-1-(2-Aminopropyl)-8,9-dihydropyrano[3,2-e]indole);

(582) AL-38022A ((S)-2-(8,9-dihydro-7H-pyrano[2,3-g]ind a zol-1-yl)-1-methylethylamine);

(583) AS-19 ((2S)—

N,N-dimethyl-5-(1,3,5-trimethylpyrazol-4-yl)-1,2,3,4-tetrahydronaphthalen-2-amine);

(584) alnespirone;

(585) BIMU8 (N-[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]-2-oxo-3-(propan-2-yl)-2,3-dihydro-1H-benzimidazole-1-carboxamide hydrochloride);

(586) BMY-14802 (1-(4-fluorophenyl)-4-[4-(5-fluoropyrimidin-2-yl)piperazin-1-yl]butan-1-ol);

(587) BRL-54443 (3-(1-methylpiperidin-4-yl)-1H-indol-5-ol);

(588) batoprazine;

(589) benzylpiperazine;

(590) binospirone;

(591) 1-(8-bromobenzo[1,2-b;

4,5-b]difuran-4-yl)-2-aminopropane);

(592) CP-809,101 (2-[(3-Chlorophenyl)methoxy]-6-(1-piperazinyl)pyrazine);

(593) CP-93,129 (3-(1,2,3,6-tetrahydropyridin-4-yl)-1,4-dihydropyrrolo[3,2-b]pyridin-5-one);

(594) CP-94,253 (3-(1,2,5,6-tetrahydro-4-pyridyl)-5-propoxypyrrolo[3,2-b]pyridine);

(595) CGS-12066A (4-(4-methylpiperazin-1-yl)-7-(trifluoromethyl)pyrrolo[1,2-a]quinoxaline);

(596) chlorophenylbiguanide;

(597) chlorphentermine;

(598) dazopride;

(599) dimemebfe;

(600) 2,5-dimethoxy-4-bromoamphetamine;

(601) 2,5-dimethoxy-4-fluoroamphetamine;

(602) 2,5-dimethoxy-4-methylamphetamine;

(603) EMD-386,088 (5-chloro-2-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole);

(604) EMDT (2-(2-ethyl-5-methoxy-1H-indol-3-yl)-N,N-dimethylethanamine);

(605) p-fluoropiperazine;

(606) fluprazine;

(607) jimscaline;

(608) LY-293,284 ((4R)-6-acetyl-4-(di-n-propylamino)-1,3,4,5-tetrahydrobenz[c,d]indole);

(609) lasmitidan;

(610) lorcaserin;

(611) 2-methyl-5-hydroxytryptamine;

(612) 2-methyl-4,5-methylenedioxyamphetamine;

(613) NBUMP(N-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]adamantane-1-carboxamide);

(614) 1-(1-naphthyl)piperazine;

(615) Org-37,684 ((3S)-3-[(2,3-dihydro-5-methoxy-1H-inden-4-yl)oxy]pyrrolidine);

(616) PNU-22394 (6-Methyl-1,2,3,4,5,6-hexahydro-azepino[4,5-b]indole));

(617) PRX-00023 (N-(3-[4-(4-cyclohexylmethanesulfonylaminobutyl)piperazin-1-yl]phenyl)acetamide);

(618) RH-34 (3-[2-(2-methoxybenzylamino)ethyl]-1H-quinazoline-2,4-dione);

(619) RS56812 (N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-2-(1-methyl-1H-indol-3-yl)-2-oxoacetamide);

(620) RS67333 (1-(4-amino-5-chloro-2-methoxyphenyl)-3-(1-butyl-4-piperidinyl)-1-propanone);

(621) RU24969 (5-Methoxy-3-(1,2,5,6-tetrahydro-4-pyridinyl)-1H-indole);

(622) Ro60-0175 ((S)-6-Chloro-5-fluoro-1H-indole-2-propanamine);

(623) TFMFly ((2R)-1-(8-trifluoromethyl-2,3,6,7-tetrahydrobenzo[1,2-b;

4,5-b′

]difuran-4-yl)-2-aminoethane);

(624) U92016-A 48R)-8-(Dipropylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-2-carbonitrile) (625) VER3323 ((2S)-1-(6-bromo-2,3-dihydroindol-1-yl)propan-2-amine);

(626) vilazodone;

(627) WAY-181,187 (1-[(2S,5S)-4,4-difluoro-5-(hydroxymethyl)tetrahydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione);

(628) WAY-208,466 (N′

-[(2Z)-4-(2,4-dichlorophenyl)-3-(2-methylpropyl)-1,3-thiazol-2(3H)-ylidene]-2-(pyrazin-2-yloxy)acetohydrazide);

(629) YM-348 (2S)-1-(7-ethyl-1H furo[2,3-g]indazol-1-yl)propan-2-amine);

(630) alprenolol;

(631) BMY 7378 (8-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-8-azaspiro[4.5]decane-7,9-dione);

(632) cyanopindolol;

(633) iodocyanopindolol;

(634) lezcotozan;

(635) methiothepin;

(636) NAN-190 (1-(2-methoxyphenyl)-4-(4-phthalimidobutyl)piperazine);

(637) oxprenolol;

(638) pindolol;

(639) propranolol;

(640) robalzotan;

(641) S15535 (1-(2,3-dihydro-1,4-benzodioxin-8-yl)-4-(2,3-dihydro-1H-inden-2-yl)piperazine);

(642) spiperone;

(643) TFMPP;

(644) UH-301 ((S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin);

(645) WAY-100,135 ((S)—

N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide);

(646) WAY-100,635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide);

(647) mefway;

(648) 5-hydroxytryptophan;

(649) 5-hydroxytryptophan creatinine sulfate complex;

(650) 5-methoxytryptamine;

(651) 5-methoxytryptamine creatinine sulfate complex;

(652) 5-HIAA (5-hydroxyindoleacetic acid); and

(653) 5-HIAA (5-hydroxyindoleacetic acid) creatinine sulfate complex; and

the salts, solvates, analogues, congeners, bioisosteres, hydrolysis products, metabolites, precursors, and prodrugs thereof.

34. The composition of claim 1 wherein the third agent is melatonin or a salt thereof.

45. The composition of claim 28 wherein the first agent is an adenosine 5′

-monophosphate-activated protein kinase (AMPK) activator and the second agent is a non-steroidal anti-inflammatory drug.

47. The composition of claim 45 wherein the third agent is selected from the group consisting of serotonin sulfate, a serotonin creatinine sulfate complex, serotonin hydrochloride, and melatonin or a salt thereof.

48. The composition of claim 1 wherein the composition comprises aspirin or a salt thereof, metformin or a salt thereof, and melatonin or a salt thereof.

49. The composition of claim 1 wherein the composition further comprises a pharmaceutically acceptable carrier.

50. The composition of claim 1 wherein the composition further comprises a liposome, wherein the composition is encapsulated by the liposome.

51. The composition of claim 1 wherein:

the first agent is selected from the group consisting of metformin or a salt thereof and a butyrate salt;

the second agent is selected from the group consisting of aspirin or a salt thereof and celecoxib or a salt thereof; and

the third agent is selected from the group consisting of melatonin or a salt thereof, serotonin creatinine sulfate complex, and serotonin hydrochloride.

2-6. -6. (canceled)

10. (canceled)

12. (canceled)

35. The composition of claim 12 wherein the second agent is a non-steroidal anti-inflammatory drug and the third agent is selected from the group consisting of serotonin sulfate, a serotonin creatinine sulfate complex, serotonin hydrochloride, and melatonin or a salt thereof.

36. The composition of claim 35 wherein the first agent is selected from the group consisting of metformin or a salt thereof, phenformin or a salt thereof, buformin or a salt thereof, and a butyrate compound selected from the group consisting of a butyrate salt and a butyrate ester.

37. The composition of claim 36 wherein the first agent is selected from the group consisting of metformin or a salt thereof and a butyrate salt.

38. The composition of claim 12 wherein the first agent is an adenosine 5′

-monophosphate-activated protein kinase (AMPK) activator and the third agent is selected from the group consisting of serotonin sulfate, a serotonin creatinine sulfate complex, serotonin hydrochloride, and melatonin or a salt thereof.

14. (canceled)

21. (canceled)

23. (canceled)

25. (canceled)

31. (canceled)

39. (canceled)

40. The composition of claim 39 wherein the first agent is selected from the group consisting of metformin or a salt thereof, phenformin or a salt thereof, buformin or a salt thereof, and butyrate or a salt thereof.

41. (canceled)

42. The composition of claim 41 wherein the second agent is acetylsalicylic acid or a salt thereof, ibuprofen or a salt thereof, or celecoxib or a salt thereof.

43-44. -44. (canceled)

46. (canceled)