Sigma receptor ligands and the use thereof

• US 6,057,371 A
• Filed: 06/10/1992
• Issued: 05/02/2000
• Est. Priority Date: 12/28/1989
• Status: Expired due to Fees

• Current Assignee: Virginia Commonwealth University
• Original Assignee: Virginia Commonwealth University
• Inventors: Glennon, Richard A.
• Primary Examiner(s): Kight, John
• Assistant Examiner(s): COVINGTON, RAYMOND K
• Application Number:
  US07/894,771
• Time in Patent Office: 2,883 Days
• Field of Search: 564/342, 564/344, 564/345, 564/347, 564/348, 564/352, 564/353, 564/354, 564/355, 564/360, 564/361, 564/366, 564/373, 564/374, 564/378, 564/381, 564/382, 564/383, 514/649, 514/651, 514/652, 514/653, 514/654, 514/655
• US Class Current: 514/649
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/215 of carboxylic acids
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/435 having six-membered rings with one nitrogen as the only ring hetero atom
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/535 having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: C07C 211/08 containing alkyl groups having a different number of carbon atoms
• CPC Class Codes: C07C 211/17 containing only non-condensed rings
• CPC Class Codes: C07C 211/27 having amino groups linked to the six-membered aromatic ring by saturated carbon chains
• CPC Class Codes: C07C 211/28 having amino groups linked to the six-membered aromatic ring by unsaturated carbon chains
• CPC Class Codes: C07C 211/29 the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
• CPC Class Codes: C07C 211/30 the six-membered aromatic ring being part of a condensed ring system formed by two rings
• CPC Class Codes: C07C 211/42 with six-membered aromatic rings being part of the condensed ring systems
• CPC Class Codes: C07C 215/52 linked by carbon chains having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
• CPC Class Codes: C07C 217/16 the six-membered aromatic ring or condensed ring system containing that ring not being further substituted
• CPC Class Codes: C07C 217/60 linked by carbon chains having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
• CPC Class Codes: C07C 219/10 : having at least one of the hydroxy groups esterified by a carboxylic acid having the esterifying carboxyl group bound to an acyclic carbon atom of a carbon skeleton containing rings
• CPC Class Codes: C07C 219/12 : having at least one of the hydroxy groups esterified by a carboxylic acid having the esterifying carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
• CPC Class Codes: C07C 225/16 : and containing six-membered aromatic rings
• CPC Class Codes: C07C 2601/02 : with a three-membered ring
• CPC Class Codes: C07C 2601/08 : the ring being saturated
• CPC Class Codes: C07C 2601/14 : The ring being saturated
• CPC Class Codes: C07C 2602/08 : the other ring being five-membered, e.g. indane
• CPC Class Codes: C07C 2602/10 : the other ring being six-membered, e.g. tetraline
• CPC Class Codes: C07C 2602/12 : the other ring being at least seven-membered
• CPC Class Codes: C07C 2603/18 : Fluorenes; Hydrogenated fluorenes
• CPC Class Codes: C07D 207/12 : Oxygen or sulfur atoms
• CPC Class Codes: C07D 209/48 : with oxygen atoms in positions 1 and 3, e.g. phthalimide
• CPC Class Codes: C07D 211/14 : with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
• CPC Class Codes: C07D 211/46 : having a hydrogen atom as the second substituent in position 4
• CPC Class Codes: C07D 211/52 : having an aryl radical as the second substituent in position 4
• CPC Class Codes: C07D 211/70 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 223/16 : Benzazepines; Hydrogenated benzazepines
• CPC Class Codes: C07D 239/42 : One nitrogen atom nitro radicals C07D239/30
• CPC Class Codes: C07D 265/30 : not condensed with other rings
• CPC Class Codes: C07D 295/03 : with the ring nitrogen atoms directly attached to acyclic carbon atoms
• CPC Class Codes: C07D 295/033 : with the ring nitrogen atoms directly attached to carbocyclic rings
• CPC Class Codes: C07D 295/073 : with the ring nitrogen atoms and the substituents separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• CPC Class Codes: C07D 295/096 : with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• CPC Class Codes: C07D 295/108 : to an acyclic saturated chain
• CPC Class Codes: C07D 295/192 : from aromatic carboxylic acids
• CPC Class Codes: C07D 317/58 : Radicals substituted by nitrogen atoms nitro radicals C07D317/52
• CPC Class Codes: C07D 471/08 : Bridged systems

Abstract

The invention relates to methods for the treatment of central nervous system disorders, gastrointestinal disorders, drug abuse, angina, migraine, hypertension and depression by administering a pharmaceutical composition comprising an effective amount of certain sigma receptor ligands to a patient in need of such treatment. The invention further relates to novel sigma receptor ligands having high binding to the sigma receptor and pharmaceutical compositions thereof. Unexpectedly, certain of the sigma receptor ligands of the present invention have selectivity for the sigma receptor over the DA, PCP and 5-HT_1A receptors.

Claims

1. A method of treating a human being suffering from a sigma receptor associated central nervous system disorder, drug abuse, gastrointestinal disorder psychosis, angina, hypertension, migraine or depression, which comprises administering to said human a therapeutically effective amount of a compound of the formula:

##STR282## wherein;

Ar is aryl, heteroaryl, substituted aryl or substituted heteroaryl, wherein the substituent is selected from the group consisting of chloro, fluoro, bromo, iodo, CF₃, C₁ -C₆ alkoxy, C₂ -C₆ dialkoxymethyl, C₁ -C₆ alkyl, cyano, C₃ -C₁₅ dialkylaminoalkyl, carboxy, carboxamido, C₁ -C₆ haloalkyl, C₁ -C₆ haloalkylthio, allyl, aralkyl, C₃ -C₆ cycloalkyl, aroyl, aralkoxy, C₂ -C₆ acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C₃ -C₆ heterocycloalkyl, C₁ -C₆ alkylthio, C₁ -C₆ alkylsulfonyl, C₁ -C₆ haloalkylsulfonyl, C₁ -C₆ alkylsulfinyl, C₁ -C₆ haloalkylsulfinyl, arylthio, C₁ -C₆ haloalkoxy, amino, C₁ -C₆ alkylamino, C₂ -C₁₅ dialkylamino, hydroxy, carbamoyl, C₁ -C₆ N-alkylcarbamoyl, C₂ -C₁₅ N,N-dialkylcarbamoyl, nitro, C₂ -C₁₅ dialkylsulfamoyl;

R is hydrogen or C₁ -C₆ alkyl;

R¹ is selected from the group consisting of hydrogen, C₁ -C₆ alkyl, C₁ -C₆ alkoxy, fluoro, chloro, bromo and =0;

or

R and R¹ together form a morpholino, piperazinyl or piperidinyl ring;

n is 0-5;

W is --(CH₂)_p -- or --H H--, wherein p is 1-3;

X is --(CH₂)_q --, wherein q is 1-6;

--(CH₂)_r --C═

C--(CH₂)_r --;

--(CH₂)_r --CH═

CH--(CH₂)_r --;

##STR283## --(CH₂)_r --Y--(CH₂)_r --, wherein each r is independently 0-3 and wherein Y is O or S;

or

C₁ -C₆ alkyl (wherein Z is hydrogen);

Z is hydrogen, cycloalkyl, aryl, an aryl-substituted carboxylic acid group, or heteroaryl wherein Z may be substituted by chloro, fluoro, bromo, iodo, CF₃, C₁ -C₆ alkoxy, C₂ -C₆ dialkoxymethyl, C₁ -C₆ alkyl, cyano, C₃ -C₁₅ dialkylaminoalkyl, carboxy, carboxamido, C₁ -C₆ haloalkyl, C₁ -C₆ haloalkylthio, allyl, aralkyl, C₃ -C₆ cycloalkyl, aroyl, aralkoxy, C₂ -C₆ carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C₃ -C₆ heterocycloalkyl, C₁ -C₆ alkylthio, C₁ -C₆ alkylsulfonyl, C₁ -C₆ haloalkylsulfonyl, C₁ -C₆ alkylsulfinyl, C₁ -C₆ haloalkylsulfinyl, arylthio, C₁ -C₆ haloalkoxy, amino, C₁ -C₆ alkylamino, C₂ -C₁₅ dialkylamino, hydroxy, carbamoyl, C₁ -C₆ N-alkylcarbamoyl, C₂ -C₁₅ N,N-dialkylcarbamoyl, nitro, C₂ -C₁₅ dialkylsulfamoyl or an ortho methylene-dioxy group;

wherein said compound exhibits high binding activity with respect to the sigma receptor.

20. The method of any one of claims 1, 2, 4, 8, 10, 12, 14, 15, 17 or 18 wherein said compound is administered as part of a pharmaceutical composition comprising a pharmaceutically acceptable carrier.

32. The method of claim 1 wherein the human being is suffering from a central nervous system disorder.

33. The method of claim 1 wherein the human being is suffering from psychiatric disorders.

34. The method of claim 1 wherein the human being is suffering from Parkinson'"'"'s disease, tardive dyskinesia or dystonias.

35. The method of claim 1 wherein the human being is suffering from drug abuse.

36. The method of claim 1 wherein the human is suffering from a gastrointestinal disorder.

37. The method of claim 1 wherein the human is suffering from depression.

62. The method of claim 1 wherein the compound exhibits low binding affinity to the dopamine receptor.

2. A method of treating a human being suffering from a sigma receptor associated central nervous system disorder, drug abuse, gastrointestinal disorder psychosis, angina, hypertension, migraine or depression, which comprises administering to said human a therapeutically effective amount of a compound of the formula:

##STR284## wherein;

R is hydrogen or C₁ -C₆ alkyl;

T is aryl, heteroaryl, substituted aryl, substituted heteroaryl, or cycloalkyl, wherein said substituent is selected from the group consisting of chloro, fluoro, bromo, iodo, CF₃, C₁ -C₆ alkoxy, C₂ -C₆ dialkoxymethyl, C₁ -C₆ alkyl, cyano, C₃ -C₁₅ dialkylaminoalkyl, carboxy, carboxamido, Cl-C₆ haloalkyl, C₁ -C₆ haloalkylthio, allyl, aralkyl, C₃ -C₆ cycloalkyl, aroyl, aralkoxy, C₂ -C₆ acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C₃ -C₆ heterocycloalkyl, C₁ -C₆ alkylthio, C₁ -C₆ alkylsulfonyl, C₁ -C₆ haloalkylsulfonyl, Cl-C₆ alkylsulfinyl, C₁ -C₆ haloalkylsulfinyl, arylthio, C₁ -C₆ haloalkoxy, amino, C₁ -C₆ alkylamino, C₂ -C₁₅ dialkylamino, hydroxy, carbamoyl, C₁ -C₆ N-alkylcarbamoyl, C₂ -C₁₅ N,N-dialkylcarbamoyl, nitro, C₂ -C₁₅ dialkylsulfamoyl, and an ortho methylenedioxy group;

R¹ is selected from the group consisting of hydrogen, C₁ -C₆ alkyl, C₁ -C₆ alkoxy, fluoro, bromo, chloro, iodo and =0;

or

R and R¹ together form a morpholino, piperazinyl or piperidinyl ring;

n is 0-5;

X is --(CH₂)_q --, wherein q is 1-6;

--(CH₂)_r --C═

C--(CH₂)_r --, wherein r is 0-3;

--(CH₂)_r --CH═

CH--(CH₂)_r --;

##STR285## --(CH₂)_r --Y--(CH₂)_r --, wherein each r is independently 0-3 and wherein Y is O or S;

or

C₁ -C₆ alkyl (wherein Z is hydrogen);

Z is hydrogen, cycloalkyl, aryl, an aryl-substituted carboxylic acid group, or aryl wherein Z may be substituted by chloro, fluoro, bromo, iodo, CF₃, C₁ -C₆ alkoxy, C₂ -C₆ dialkoxymethyl, C₁ -C₆ alkyl, cyano, C₃ -C₁₅ dialkylaminoalkyl, carboxy, carboxamido, C₁ -C₆ haloalkyl, C₁ -C₆ haloalkylthio, allyl, aralkyl, C₃ -C₆ cycloalkyl, aroyl, aralkoxy, C₂ -C₆ carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C₃ -C₆ heterocycloalkyl, C₁ -C₆ alkylthio, C₁ -C₆ alkylsulfonyl, C₁ -C₆ haloalkylsulfonyl, C₁ -C₆ alkylsulfinyl, C₁ -C₆ haloalkylsulfinyl, arylthio, C₁ -C₆ haloalkoxy, amino, C₁ -C₆ alkylamino, C₂ -C₁₅ dialkylamino, hydroxy, carbamoyl, C₁ -C₆ N-alkylcarbamoyl, C₂ -C₁₅ N,N-dialkylcarbamoyl, nitro, C₂ -C₁₅ dialkylsulfamoyl, or an ortho methylene-dioxy group;

wherein said compound exhibits high binding activity with respect to the sigma receptor.

3. The method of claim 2, wherein said compound is selected from the group consisting of N-phenethyl-1-phenylisopropylamine, N-(3-phenylpropyl)-1-phenyl-isopropylamine, N-(2-phenoxy)ethyl)-1-phenylisopropylamine, N-(3-phenyl-3-propanon-1-yl)-1-phenylisopropylamine, N-(4-phenylbutyl)-1-phenylisopropylamine, N-(3-(1-naphthyl)propyl)-1-phenylisopropylamine,N-(3-(2-naphthyl)propyl)-1-phenylisopropylamine, N-methyl-N-(3-(2-naphthyl)propyl)-1-phenylisopropylamine, N-(3-phenyl-2-propyn-1-yl)-1-phenyl-isopropylamine, N-(3-phenylpropyl)-1-(4-hydroxyphenyl)isopropylamine,N-(3-phenylpropyl)-1-(4-methoxyphenyl)isopropylamine, N-(3-phenylpropyl)-1-(3-bromophenyl)isopropylamine, N-(3-phenylpropyl)-1-(4-bromophenyl)isopropylamine, N-(3-phenylpropyl)-1-(3,4-dichlorophenyl)isopropylamine, N-(3-phenylpropyl)-1-(4-iodophenylisopropyl)-amine, N-(3-phenylpropyl)-1-(3-trifluoromethylphenyl)isopropylamine, N-(2-phenethyl)-N-methyl-1-phenylisopropylamine, N-(3-phenylpropyl)-1-phenylpropan-1-one-2-amine, N-(2-indanyl)-3-phenylpropylamine,N,N-di-(3-phenylpropyl)amine, N-(2-(1-naphthyl)ethyl)-1-phenylisopropylamine, N-(2-(2-naphthyl)ethyl)-1-phenylisopropylamine, N-(2-(1-naphthyl)propyl)-1-phenylisopropylamine, N-(2-(2-naphthyl)propyl)-1-phenylisopropylamine, N-(4-phenylbutyl)-1-(2,5-dimethoxyphenyl)isopropylamine, N-(4-phenylbutyl)-1-(4-bromo-2,5-dimethoxyphenyl)isopropylamine, N-methyl-N-(4-phenylbutyl)-1-phenylisopropylamine, N-methyl-N-(5-phenylpentyl)-1-phenylisopropylamine, N-(3-phenylpropyl)-1-(4-ethoxyphenyl)isopropyl-amine, N-(3-phenylpropyl)-1-(4-propylphenyl)isopropylamine, N-(3-phenylpropyl)-1-(4-benzoxyphenyl)isopropylamine, N-methyl-N-(3-phenylpropyl)-1-(4-propylphenyl)isopropylamine, N-(3-phenylpropyl)-1-phenyl-2-pentylamine,N-(4-phenylbutyl)-1-phenyl-2-pentylamine,N,N-di-(2-ethylphenyl)methylamine,N,N-dibenzylamine,N-(3-phenylpropyl)-N-(6-phenylhexyl)amine, N-(3-phenylpropyl)-N-(5-phenylpentyl)amine, N-propyl-N-methyl-5-phenylpentylamine, N-methyl-N-(3-phenylpropyl)-1-phenyl isopropylamine, N-methyl -N-(3-methyl-2-butenyl)-1-phenyliso-propylamine, N-methyl-N-(3-methylbutyl)-1-phenylisopropylamine, N-methyl-N-(3-phenylpropyl)-1-phenyl-2-pentylamine, N-methyl-N-(3-methylbutyl)-1-isopropylamine, N-methyl-N-(3-phenylbutyl)-1-phenyl-2-pentylamine, N-propyl-N-(3-phenyl)propyl)-1-phenyl-2-propylamine, N-benzyl-N-(3-phenyl)-propyl)-1-phenyl-2-propylamine, N-phenyl-(5-phenyl)pentylamine, N-methyl-N-(3-phenyl)propyl-5-phenylpentylamine,N-(2-(o-methylphenyl)ethyl)-5-phenylpentylamine, N-(2-(m-methylphenyl)ethyl)-5-phenylpentylamine, N-(2-(p-methylphenyl)ethyl)-5-phenylpentylamine, N-benzyl-5-phenylpentylamine, N-benzyl-N-methyl-5-phenyl-pentylamine,N-(2-(3-hydroxyphenyl)ethyl)-5-phenylpentylamine,N-(2-(2-hydroxyphenyl)ethyl)-5-phenylpentylamine, N,N'"'"'-diethyl-2-(diphenylacetoxy)ethylamine,N,N'"'"'-diethyl-2-(9-fluorenecarboxy)-ethylamine, N,N-Dimethyl-5-phenylpentylamine, N-Benzyl-N-(3-phenylpropyl)-1-phenyl-2-propylamine, N-Benzyl-N-methyl-5-phenylpentylamine, N-Benzyl-5-phenylpentylamine, and N-(2-phenethyl)-N-methylpentylamine.

21. The method of claim 2 where T is phenyl or substituted phenyl, R¹ is independently hydrogen or C₁ -C₆ alkyl, X is --(CH₂)_q -- and Z is hydrogen, cycloalkyl or aryl.

22. The method of claim 21 where Z is hydrogen, cycloalkyl or phenyl.

23. The method of claim 21 where T is phenyl, n and q are each 2, R is C_1-6 alkyl, and Z is phenyl.

24. The method of claim 2, where T is phenyl or substituted phenyl, R¹ is independently hydrogen or C₁ -C₆ alkyl, X is --(CH₂)_r --CH═

CH--(CH₂)_r --, and Z is hydrogen, cycloalkyl or aryl.

25. The method of claim 24 where Z is hydrogen, cycloalkyl or phenyl.

26. The method of claim 25 where R is C₁ -C₆ alkyl.

27. The method of claim 2 where T is phenyl, R and R¹ are each hydrogen, X is --(CH₂)_q -- and cycloalkyl.

28. The method of claim 27 where n is 1 and q is 4.

29. The method of claim 2 where T is phenyl, R¹ is hydrogen, R is C₁ -C₆ alkyl, X is --(CH₂)_q -- and Z is hydrogen.

30. The method of claim 29 where n is 5, and q is 3.

31. The method of claim 30 where R is methyl.

38. The method of claim 2 wherein the human being is suffering from a central nervous system disorder.

39. The method of claim 2 wherein the human being is suffering from psychiatric disorders.

40. The method of claim 2 wherein the human being is suffering from Parkinson'"'"'s disease, tardive dyskinesia or dystonias.

41. The method of claim 2 wherein the human being is suffering from drug abuse.

42. The method of claim 2 wherein the human is suffering from a gastrointestinal disorder.

43. The method of claim 2 wherein the human is suffering from depression.

44. The method of claim 21 wherein the human being is suffering from a central nervous system disorder.

45. The method of claim 21 wherein the human being is suffering from psychiatric disorders.

46. The method of claim 21 wherein the human being is suffering from Parkinson'"'"'s disease, tardive dyskinesia or dystonias.

47. The method of claim 21 wherein the human being is suffering from drug abuse.

48. The method of claim 21 wherein the human is suffering from a gastrointestinal disorder.

49. The method of claim 21 wherein the human is suffering from depression.

50. The method of claim 24 wherein the human being is suffering from a central nervous system disorder.

51. The method of claim 24 wherein the human being is suffering from psychiatric disorders.

52. The method of claim 24 wherein the human being is suffering from Parkinson'"'"'s disease, tardive dyskinesia or dystonias.

53. The method of claim 24 wherein the human being is suffering from drug abuse.

54. The method of claim 24 wherein the human is suffering from a gastrointestinal disorder.

55. The method of claim 24 wherein the human is suffering from depression.

56. The method of claim 29 wherein the human being is suffering from a central nervous system disorder.

57. The method of claim 29 wherein the human being is suffering from psychiatric disorders.

58. The method of claim 29 wherein the human being is suffering from Parkinson'"'"'s disease, tardive dyskinesia or dystonias.

59. The method of claim 29 wherein the human being is suffering from drug abuse.

60. The method of claim 29 wherein the human is suffering from a gastrointestinal disorder.

61. The method of claim 29 wherein the human is suffering from depression.

63. The method of claim 2 wherein the compound exhibits low binding affinity to the dopamine receptor.

4. A method of treating a human being suffering from a sigma receptor associated central nervous system disorder, drug abuse, gastrointestinal disorder psychosis, angina, hypertension, migraine or depression, which comprises administering to said, human a therapeutically effective amount of a compound of the formula:

##STR286## wherein;

R is hydrogen or C₁ -C₆ alkyl;

Ar is aryl, heteroaryl, substituted aryl or substituted heteroaryl, wherein the substituent is selected from the group consisting of chloro, fluoro, bromo, iodo, CF₃, C₁ -C₆ alkoxy, C₂ -C₆ dialkoxymethyl, C₁ -C₆ alkyl, cyano, C₃ -C₁₅ dialkylaminoalkyl, carboxy, carboxamido, C₁ -C₆ haloalkyl, C₁ -C₆ haloalkylthio, allyl, aralkyl, C₃ -C₆ cycloalkyl, aroyl, aralkoxy, C₂ -C₆ acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C₃ -C₆ heterocycloalkyl, C₁ -C₆ alkylthio, C₁ -C₆ alkylsulfonyl;

C₁ -C₆ haloalkylsulfonyl, C₁ -C₆ alkylsulfinyl, C₁ -C₆ haloalkylsulfinyl, arylthio, C₁ -C₆ haloalkoxy, amino, C₁ -C₆ alkylamino, C₂ -C₁₅ dialkylamino, hydroxy, carbamoyl, C₁ -C₆ N-alkylcarbamoyl, C₂ -C₁₅ N,N-dialkylcarbamoyl, nitro and C₂ -C₁₅ dialkylsulfamoyl;

R¹ is selected from the group consisting of hydrogen, C₁ -C₆ alkyl, C₁ -C₆ alkoxy, fluoro, chloro, bromo, iodo and =0;

or

R and R¹ together form a morpholino, piperazinyl or piperidinyl ring;

n is 1-3;

p is 1-3;

X is --(CH₂)_q --, wherein q is 1-6;

--(CH₂)_r --C═

C--(CH₂)_r --;

--(CH₂)_r --CH=CH--(CH₂)_r --, ##STR287## --(CH₂)_r --Y--(CH₂)_r --, wherein each r is independently 0-3 and wherein Y is O or S;

or

C₁ -C₆ alkyl;

Z is hydrogen, cycloalkyl, aryl or heteroaryl wherein Z may be substituted by chloro, fluoro, bromo, iodo, CF₃, C₁ -C₆ alkoxy, C₂ -C₆ dialkoxymethyl, C₁ -C₆ alkyl, cyano, C₃ -C₁₅ dialkylaminoalkyl, carboxy, carboxamido, C₁ -C₆ haloalkyl, C₁ -C₆ haloalkylthio, allyl, aralkyl, C₃ -C₆ cycloalkyl, aroyl, aralkoxy, C₂ -C₆ carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C₃ -C₆ heterocycloalkyl, C₁ -C₆ alkylthio, C₁ -₆ alkylsulfonyl, C₁ -C₆ haloalkylsulfonyl, C₁ -C₆ alkyl-sulfinyl, C₁ -C₆ haloalkylsulfinyl, arylthio, C₁ -C₆ haloalkoxy, amino, C₁ -C₆ alkylamino, C₂ -C₁₅ dialkylamino, hydroxy, carbamoyl, C₁ -C₆ N-alkylcarbamoyl, C₂ -C₁₅ N,N-dialkylcarbamoyl, nitro, C₂ -C₁₅ dialkylsulfamoyl or methylenedioxy;

wherein said compound exhibits a high binding activity with respect to the sigma receptor.

5. The method of claim 4, wherein said compound is selected from the group consisting of N-(2-indanyl)-1-phenylisopropylamine, N-(2-indanyl)-3-phenylpropylamine, N-(4,5-benzocycloheptyl)-1-phenylisopropylamine, N-(3,4-benzocycloheptyl)-3-(phenyl)propylamine, N-(4,5-benzocycloheptyl)-3-phenylpropylamine, N-(3,4-benzocyclohexyl)-1-phenylisopropylamine and N-3,4-benzocyclohexyl-3-phenylpropylamine.

64. The method of claim 4 wherein the compound exhibits low binding affinity to the dopamine receptor.

6. A method of treating a human being suffering from a sigma receptor associated central nervous system disorder, drug abuse, gastrointestinal disorder, psychosis, angina, hypertension, migraine or depression, which comprises administering to said human a therapeutically effective amount of a compound of the formula:

##STR288## wherein;

R⁴ is hydrogen or an aryl group substituted with a group selected from the group consisting of C₁ -C₆ alkyl, C₁ -C₆ alkenyl, C₂ -C₆ dialkoxymethyl, C₃ -C₁₅ dialkylaminoalkyl, aralkyl, C₃ -C₆ cycloalkyl, aroyl, C₂ -C₆ acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C₃ -C₆ heterocycloalkyl;

R⁵ is hydrogen or hydroxy;

X is --(CH₂)_q --, wherein q is 1-6;

--(CH₂)_r --C═

C--(CH₂)_r --,

--(CH₂)_r --CH═

CH--(CH₂)_r --;

##STR289## --(CH₂)_r --Y--(CH₂)_r --, wherein each r is independently 0-3 and wherein Y is O or S;

or

C₁ -C₆ alkyl (wherein Z is hydrogen);

Z is cycloalkyl, aryl or heteroaryl wherein Z may be substituted by chloro, fluoro, bromo, iodo, CF₃, C₁ -C₆ alkoxy, C₂ -C₆ dialkoxymethyl, C₁ -C₆ alkyl, cyano, C₃ -C₁₅ dialkylaminoalkyl, carboxy, carboxamido, C₁ -C₆ haloalkyl, C₁ -C₆ haloalkylthio, allyl, aralkyl, C₃ -C₆ cycloalkyl, aroyl, aralkoxy, C₂ -C₆ carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C₃ -C₆ heterocycloalkyl, C₁ -C₆ alkylthio, C₁ -C₆ alkylsulfonyl, C₁ -C₆ haloalkylsulfonyl, C₁ -C₆ alkylsulfinyl, C₁ -C₆ haloalkylsulfinyl, arylthio, C₁ -C₆ haloalkoxy, amino, C₁ -C₆ alkyl-amino, dialkylamino, hydroxy, carbamoyl, C₁ -C₆ N-alkylcarbamoyl, C₂ -C₁₅ N,N-dialklcarbamoyl, nitro, C₂ -C₁₅ dialkylsulfamoyl or methylenedioxy;

wherein said compound exhibits a high binding activity with respect to the sigma receptors.

7. The method of claim 6, wherein said compound is selected from the group consisting of N-(5-phenylpentyl)-piperidine, N-(8-phenylheptyl)piperidine, N-(5-(4-methoxyphenyl)pentyl)piperidine, N-(3-phenylpropyl)piperidine,N-(5-cyclohexyl)pentylpiperidine, N-benzylpiperidine, N-(2-phenethyl)-4-hydroxy-4-phenylpiperidine, N-(2-phenethyl)-4-hydroxy-4-t-butylpiperidine,N-(5-(4-chlorophenyl)-5-pentanon-1-yl)piperidine, N-(5-(4-chlorophenyl)-5-pentanon-1-yl)-4-phenylpiperidine,N-(5-(4-methoxyphenyl)-5-pentanon-1-yl)piperidine,N-(5-(4-methoxyphenyl)-5-pentanon-1-yl)-4-phenylpiperidine, N-(5-(4-methoxyphenyl)pentyl)-4-phenylpiperidine, N-(5-phenyl-5-pentanon-1-yl)-4-phenylpiperidine, N-(5-(4-chlorophenyl)-pentyl)-4-phenylpiperidine, N-(5-(3-methoxyphenyl)-5-pentanon-1-yl)piperidine,N-(5-(3-chlorophenyl)-5-pentanon-1-yl)piperidine, N-(5-(3-chlorophenyl)-5-pentanon-1-yl)-4-phenylpiperidine,N-(5-(3-methoxyphenyl)-5-pentanon-1-yl)-4-phenylpiperidine, N-(4-(4-fluorophenyl)-4-butanon-1-yl)piperidine, N-(5-(4-fluorophenyl)-5-pentanon-1-yl)piperidine, N-(5-(4-fluorophenyl)-5-pentanon-1-yl)-4-phenylpiperidine,N-(5-(4-fluorophenyl)-5-pentanon-1-yl)-4-(3-chlorophenyl)-4-hydroxypiperidine, N-(5-(4-chlorophenyl)-5-pentanon-1-yl)-4-(4-fluorophenyl)-1,2,3,6-terahydropyridine, N-(5-(4-chlorophenyl)-5-pentanon-1-yl)-4-(4-fluorophenyl)-piperidine, N-(5-(4-chlorophenyl)-5-pentanon-1-yl)-4-(4-fluorophenyl)-1,2,3,6-terahydropyridine, N-(5-(4-chlorophenyl)-5-pentanon-1-yl)-4-(4-fluorophenyl)-piperidine, N-(S-(4-chlorophenyl)-5-pentanon-1-yl)-4-(chlorophenyl)-1,2,3,6-terahydropyridine, N-(5-(4-chlorophenyl)-5-pentanon-1-yl)-4-(chlorophenyl)piperidine, N-(5-(3,4-dichlorophenyl)-5-pentanon-1-yl)-4-(chlorophenyl)-piperidine, N-(5-cyclopentylpentan-5-on-1-yl)piperidine and N-(5-(3,4-methylenedioxyphenyl)penta-2,4-dienyl)piperidine.

65. The method of claim 6 wherein the compound exhibits low binding affinity to the dopamine receptor.

8. A method of treating a human being suffering from a sigma reception associated central nervous system disorder, drug abuse, gastrointestinal disorder, psychosis, angina, hypertension, migraine or depression, which comprises administering to said human a therapeutically effective amount of a compound having the formula:

##STR290## wherein, X is --(CH₂)_q --, wherein q is 1-6,

--(CH₂)_r --C═

C--(CH₂)_r --;

--(CH₂)_r --CH═

CH--(CH₂)_r --;

##STR291## --(CH₂)_r --Y--(CH₂)_r --, wherein each r is independently 0-3 and wherein Y is O or S;

or

C₁ -C₆ alkyl (wherein Z is hydrogen);

Z is cycloalkyl, aryl or heteroaryl wherein Z may be substituted by chloro, fluoro, bromo, iodo, CF₃, C₁ -C₆ alkoxy, C₂ -C₆ dialkoxymethyl, C₁ -C₆ alkyl, cyano, C₃ -C₁₅ dialkylaminoalkyl, carboxy, carboxamido, C₁ -C₆ haloalkyl, C₁ -C₆ haloalkylthio, allyl, aralkyl, C₃ -C₆ cycloalkyl, aroyl, aralkoxy, C₂ -C₆ carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C₃ -C₆ heterocycloalkyl, C₁ -C₆ alkylthio, C₁ -C₆ alkylsulfonyl, C₁ -C₆ haloalkylsulfonyl, C₁ -C₆ alkylsulfinyl, C₁ -C₆ haloalkylsulfinyl, arylthio, C₁ -C₆ haloalkoxy, amino, C₁ -C₆ alkyl-amino, dialkylamino, hydroxy, carbamoyl, C₁ -C₆ N-alkylcarbamoyl, C₂ -C₁₅ N,N-dialklcarbamoyl, nitro, C₂ -C₁₅ dialkylsulfamoyl or methylenedioxy;

wherein said compound exhibits a high binding activity with respect to the sigma receptors.

9. The method of claim 8, wherein said compound is N-(5-phenyl)pentyl-3-azabicyclo[3.2.2]nonane.

66. The method of claim 8 wherein the compound exhibits low binding affinity to the dopamine receptor.

10. A method of treating a human being suffering from a sigma receptor associated central nervous system disorder, drug abuse, gastrointestinal disorder, psychosis, angina, hypertension, migraine or depression, which comprises administering to said human a therapeutically effective amount of a compound of the formula:

##STR292## wherein a is 1-8;

b is 1-8;

R is hydrogen or C₁ -C₆ alkyl;

R² is independently selected from the group consisting of hydrogen, chloro, fluoro, bromo, iodo, CF₃, C₁ -C₆ alkoxy, C₂ -C₆ dialkoxymethyl, C₁ -C₆ alkyl, cyano, C₃ -C₁₅ dialkylaminoalkyl, carboxy, carboxamido, C₁ -C₆ haloalkyl, C₁ -C₆ haloalkylthio, allyl, aralkyl, C₃ -C₆ cycloalkyl, aroyl, aralkoxy, C₂ -C₆ carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C₃ -C₆ heterocycloalkyl, C₁ -C₆ alkylthio, C₁ -C₆ alkylsulfonyl, C₁ -C₆ haloalkylsulfonyl, C₁ -C₆ alkylsulfinyl, C₁ -C₆ haloalkylsulfinyl, arylthio, C₁ -C₆ haloalkoxy, amino, C₁ -C₆ alkylamino, dialkylamino, hydroxy, carbamoyl, C₁ -C₆ N-alkylcarbamoyl, C₂ -C₁₅ N,N-dialklcarbamoyl, nitro and C₂ -C₁₅ dialkylsulfamoyl;

wherein said compound exhibits high binding activity with respect to the sigma receptor.

11. The method of claim 10 wherein said compound is selected from the group consisting of N-(4-phenylbutyl)phenethyl-amine, N-(4-phenylbutyl)-3-phenylpropylamine, N-(4-phenylbutyl)-4-phenylbutylamine, N-(4-phenylbutyl)benzylamine, N-(4-phenylbutyl)-5-phenylpentylamine,N-(5-phenylpentyl)benzylamine, N-(3-phenylpropyl)phenethylamine, N-(5-phenylpentyl)phenethylamine, N-(7-phenylheptyl)benzylamine, N-(7-phenylheptyl)phenethylamine,N-methyl-N-(2-phenethyl)-1-phenylisopropylamine, N-methyl-N-(5-phenylpentyl)-1-phenylisopropylamine, N-methyl-N-(3-phenylpropyl)-1-(4-propylphenyl)isopropylamine, N-phenyl-(5-phenyl)pentylamine, N-methyl-N-(3-phenylpropyl)-5-phenylpentylamine, N-benzyl-N-methyl-5-phenylpentylamine, N-(2-(o-methoxyphenyl)ethyl)-5-phenylpentylamine, N-(2-(m-methoxyphenyl)ethyl)-5-phenylpentylamine,N-(2-(p-methoxyphenyl)ethyl)-5-phenylpentylamine, N-benzyl-5-phenylpentylamine, N-(2-(m-hydroxyphenyl)ethyl)-5-phenylpentylamine, and N-(2-(o-hydroxyphenyl)ethyl)-5-phenylpentylamine.

67. The method of claim 10 wherein the compound exhibits low binding affinity to the dopamine receptor.

12. A method of treating a human being suffering from a sigma receptor associated central nervous system disorder, drug abuse, gastrointestinal disorder, psychosis, angina, hypertension, migraine or depression, which comprises administering to said human a therapeutically effective amount of a compound having the Formula:

##STR293## wherein a is 1-8;

b is 1-8;

R is hydrogen or C₁ -C₆ alkyl;

R² is independently selected from the group consisting of hydrogen, chloro, fluoro, bromo, iodo, CF₃, C₁ -C₆ alkoxy, C₂ -C₆ dialkoxymethyl, C₁ -C₆ alkyl, cyano, C₃ -C₁₅ dialkylaminoalkyl, carboxy, carboxamido, C₁ -C₆ haloalkyl, C₁ -C₆ haloalkylthio, allyl, aralkyl, C₃ -C₆ cycloalkyl, aroyl, aralkoxy, C₂ -C₆ carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C₃ -C₆ heterocycloalkyl, C₁ -C₆ alkylthio, C₁ -C₆ alkylsulfonyl, C₁ -C₆ haloalkylsulfonyl, C₁ -C₆ alkylsulfinyl, C₁ -C₆ haloalkylsulfinyl, arylthio, C₁ -C₆ haloalkoxy, amino, C₁ -C₆ alkyl-amino, dialkylamino, hydroxy, carbamoyl, C₁ -C₆ N-alkylcarbamoyl, C₂ -C₁₅ N,N-dialklcarbamoyl, nitro and C₂ -C₁₅ dialkylsulfamoyl; and

wherein said compound exhibits high binding activity with respect to the sigma receptor.

13. The method of claim 12, wherein said compound is N-(3-phenylpropyl)-2-(2-naphthyl)ethylamine.

68. The method of claim 12 wherein the compound exhibits low binding affinity to the dopamine receptor.

14. A method of treating a human being suffering from a sigma receptor associated central nervous system disorder, drug abuse, gastrointestinal disorder psychosis, angina, hypertension, migraine or depression, which comprises administering to said human a therapeutically effective amount of a compound having the formula:

##STR294## wherein;

Ar is aryl, heteroaryl, substituted aryl or substituted heteroaryl, wherein the substituent is selected from the group consisting of chloro, fluoro, bromo, iodo, CF₃, C₁ -C₆ alkoxy, C₂ -C₆ dialkoxymethyl, C₁ -C₆ alkyl, cyano, C₃ -C₁₅ dialkylaminoalkyl, carboxy, carboxamido, C₁ -C₆ haloalkyl, C₁ -C₆ haloalkylthio, allyl, aralkyl, C₃ -C₆ cycloalkyl, aroyl, aralkoxy, C₂ -C₆ acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C₃ -C₆ heterocycloalkyl, C₁ -C₆ alkylthio, C₁ -C₆ alkylsulfonyl, C₁ -C₆ haloalkylsulfonyl, C₁ -C₆ alkylsulfinyl, C₁ -C₆ haloalkylsulfinyl, arylthio, C₁ -C₆ haloalkoxy, amino, C₁ -C₆ alkylamino, C₂ -C₁₅ dialkylamino, hydroxy, carbamoyl, C₁ -C₆ N-alkylcarbamoyl, C₂ -C₁₅ N,N-dialkylcarbamoyl, nitro and C₂ -C₁₅ dialkylsulfamoyl;

X is --(CH₂)_q --, wherein q is 1-6;

--(CH₂)_r --CH═

C--(CH₂)_r --;

--(CH₂)_r --CH═

CH--(CH₂)_r --;

##STR295## --(CH₂)_r --Y--(CH₂)_r --, wherein each r is independently 0-3 and wherein Y is O or S;

or

C₁ -C₆ alkyl;

Z is hydrogen, cycloalkyl, aryl or heteroaryl wherein Z may be substituted by chloro, fluoro, bromo, iodo, CF₃, C₁ -C₆ alkoxy, C₂ -C₆ dialkoxymethyl, C₁ -C₆ alkyl, cyano, C₃ -C₁₅ dialkylaminoalkyl, carboxy, carboxamido, C₁ -C₆ haloalkyl, C₁ -C₆ haloalkylthio, allyl, aralkyl, C₃ -C₆ cycloalkyl, aroyl, aralkoxy, C₂ -C₆ carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C₃ -C₆ heterocycloalkyl, C₁ -C₆ alkylthio, C₁ -C₆ alkylsulfonyl, C₁ -C₆ haloalkylsulfonyl, C₁ -C₆ alkylsulfinyl, C₁ -C₆ haloalkylsulfinyl, arylthio, C₁ -C₆ haloalkoxy, amino, C₁ -C₆ alkylamino, C₂ -C₁₅ dialkylamino, hydroxy, carbamoyl, C₁ -C₆ N-alkylcarbamoyl, C₂ -C₁₅ N,N-dialkylcarbamoyl, nitro, C₂ -C₁₅ dialkylsulfamoyl or methylenedioxy;

wherein said compound exhibits high binding activity with respect to the sigma receptor.

69. The method of claim 14 wherein the compound exhibits low binding affinity to the dopamine receptor.

15. A method of treating a human being suffering from a sigma receptor associated central nervous system disorder, drug abuse, gastrointestinal disorder, psychosis, angina, hypertension, migraine or depression, which comprises administering to said human a therapeutically effective amount of a compound having the formula:

##STR296## wherein n is 0-5;

Cy is C₃ -C₈ cycloalkyl;

R is hydrogen or C₁ -C₆ alkyl;

R¹ is independently selected from the group consisting of hydrogen, C₁ -C₆ alkyl, C₁ -C₆ alkoxy, fluoro, chloro, bromo, iodo and =0;

X is --(CH₂)_q --, wherein q is 1-6;

--(CH₂)_r --C═

C--(CH₂)_r --, wherein r is 0-3;

--(CH₂)_r --CH═

CH--(CH₂)_r --;

##STR297## --(CH₂)_r --Y--(CH₂)_r --, wherein each r is independently 0-3 and wherein Y is O or S;

or

C₁ -C₆ alkyl (wherein Z is hydrogen); and

Z is hydrogen, cycloalkyl, aryl or heteroaryl wherein Z may be substituted by chloro, fluoro, bromo, iodo, CF₃, C₁ -C₆ alkoxy, C₂ -C₆ dialkoxymethyl, C₁ -C₆ alkyl, cyano, C₃ -C₁₅ dialkylaminoalkyl, carboxy, carboxamido, C₁ -C6 haloalkyl, C₁ -C₆ haloalkylthio, allyl, aralkyl, C₃ -C₆ cycloalkyl, aroyl, aralkoxy, C₂ -C₆ carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C₃ -C₆ heterocycloalkyl, C₁ -C₆ alkylthio, C₁ -C₆ alkylsulfonyl, C₁ -C₆ haloalkylsulfonyl, C₁ -C₆ alkylsulfinyl, C₁ -C₆ haloalkylsulfinyl, arylthio, C₁ -C₆ haloalkoxy, amino, C₁ -C₆ alkylamino, C₂ -C₁₅ dialkylamino, hydroxy, carbamoyl, C₁ -C₆ N-alkylcarbamoyl, C₂ -C₁₅ N,N-dialkylcarbamoyl, nitro, C₂ -C₁₅ dialkylsulfamoyl or methylenedioxy;

wherein said compound exhibits high binding activity with respect to the sigma receptor.

16. The method of claim 15, wherein said compound is selected from the group consisting of N-(3-cyclohexylpropyl)-3-phenylpropylamine, N-cyclohexylmethyl-3-phenylpropylamine, N-(5-cyclohexylpentyl)benzylamine, 5-cyclohexylpentylamine, N-methyl-5-cyclohexylpentylamine, N,N-Dimethyl-5-cyclohexylpentylamine, N-cyclohexylmethyl-5-cyclohexyl-n-pentylamine, and N-cyclohexylmethyl-N-methyl-5-cyclohexyl-n-pentylamine.

70. The method of claim 15 wherein the compound exhibits low binding affinity to the dopamine receptor.

17. A method of treating a human being suffering from a sigma receptor associated central nervous system disorder, psychosis, angina, hypertension, migraine drug abuse, gastrointestinal disorder or depression, which comprises administering to said human a therapeutically effective amount of a compound having the formula:

##STR298## wherein X¹ is --(CH₂)_r --C═

C--(CH₂)_r --, wherein each r is 0-3 independently;

--(CH₂)_r --CH═

CH--(CH₂)_r --;

##STR299## --(CH₂)_r --Y--(CH₂)_r --, wherein Y is O or S;

or C₁ -C₆ alkyl (wherein Z is hydrogen);

R² is independently selected from the group consisting of hydrogen, chloro, fluoro, bromo, iodo, CF₃, C₁ -C₆ alkoxy, C₂ -C₆ dialkoxymethyl, C₁ -C₆ alkyl, cyano, C₃ -C₁₅ dialkylaminoalkyl, carboxy, carboxamido, C₁ -C₆ haloalkyl, C₁ -C₆ haloalkylthio, allyl, aralkyl, C₃ -C₆ cycloalkyl, aroyl, aralkoxy, C₂ -C₆ carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C₃ -C₆ heterocycloalkyl, C₁ -C₆ alkylthio, C₁ -C₆ alkylsulfonyl, C₁ -C₆ haloalkylsulfonyl, C₁ -C₆ alkylsulfinyl, C₁ -C₆ haloalkylsulfinyl, arylthio, C₁ -C₆ haloalkoxy, amino, C₁ -C₆ alkyl-amino, dialkylamino, hydroxy, carbamoyl, C₁ -C₆ N-alkylcarbamoyl, C₂ -C₁₅ N,N-dialkicarbamoyl, nitro and C₂ -C₁₅ dialkylsulfamoyl;

V is N or CM, wherein M is hydrogen, C₁ -C₆ alkyl, C₁ -C₆ alkoxy, fluoro, chloro, bromo, trifluoromethyl, hydroxy or one half of a double bond with the neighboring endocyclic carbon;

X is --(CH₂)q-l wherein q is 1-6;

--(CH₂)_r --C═

C--(CH₂)_r --, wherein r is 0-3;

--(CH₂)_r --CH═

CH--(CH₂)_r --;

##STR300## --(CH₂)_r --Y--(CH₂)_r --, wherein each r is independently 0-3 and wherein Y is O or S;

or

C₁ -C₆ alkyl (wherein Z is hydrogen); and

Z is hydrogen, cycloalkyl, aryl or heteroaryl wherein Z may be substituted by chloro, fluoro, bromo, iodo, CF₃, C₁ -C₆ alkoxy, C₂ -C₆ dialkoxymethyl, C₁ -C₆ alkyl, cyano, C₃ -C₁₅ dialkylaminoalkyl, carboxy, carboxamido, C₁ -C₆ haloalkyl, C₁ -C₆ haloalkylthio, allyl, aralkyl, C₃ -C₆ cycloalkyl, aroyl, aralkoxy, C₂ -C₆ carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C₃ -C₆ heterocycloalkyl, C₁ -C₆ alkylthio, C₁ -C₆ alkylsulfonyl, C₁ -C₆ haloalkylsulfonyl, C₁ -C₆ alkylsulfinyl, C₁ -C₆ haloalkylsulfinyl, arylthio, C₁ -C₆ haloalkoxy, amino, C₁ -C₆ alkylamino, C₂ -C₁₅ dialkylamino, hydroxy, carbamoyl, C₁ -C₆ N-alkylcarbamoyl, C₂ -C₁₅ N,N-dialkylcarbamoyl, nitro and C₂ -C₁₅ dialkylsulfamoyl;

wherein said compound exhibits high binding activity with respect to the sigma receptor.

71. The method of claim 17 wherein the compound exhibits low binding affinity to the dopamine receptor.

18. A method of treating a human being suffering from a sigma receptor associated central nervous system disorder, drug abuse, gastrointestinal disorder psychosis, angina, hypertension, migraines or depression, which comprises administering to said human a therapeutically effective amount of a compound having the formula:

##STR301## wherein R⁵ and R⁶ are independently a C_1-8 alkyl group;

R⁷ is hydrogen or a C_1-8 alkyl group substituted by an arylacetoxy or arylcarboxy group; and

X is --(CH₂)_q --, wherein q is 1-6;

--(CH₂)_r --C═

C--(CH₂)_r --, wherein r is 0-3;

--(CH₂)_r --CH═

CH--(CH₂)_r --;

##STR302## --(CH₂)_r --Y--(CH₂)_r --, wherein each r is independently 0-3 and wherein Y is O or S;

or

C₁ -C₆ alkyl (wherein R⁷ is hydrogen);

wherein said compound exhibits a high binding activity with respect to the sigma receptors.

19. The method of claim 18, wherein said compound is selected from the group consisting of N,N-dimethyl-n-hexylamine, N-methyl-N-propylhexylamine, N,N'"'"'-diethyl-2-(diphenylacetoxy)ethylamine, and N,N'"'"'-diethyl-2-(9-fluorenecarboxy)ethylamine.

72. The method of claim 18 wherein the compound exhibits low binding affinity to the dopamine receptor.