Treatment for a attention-deficit hyperactivity disorder

• US 20050004105A1
• Filed: 01/29/2004
• Published: 01/06/2005
• Est. Priority Date: 01/29/2003
• Status: Abandoned Application

• Current Assignee: Psychogencis, Inc.
• Original Assignee: Psychogencis, Inc.
• Inventors: Olivier, Berend, Leahy, Emer
• Application Number:
  US10/767,788
• Publication Number:
  US 20050004105A1
• Time in Patent Office: Days
• US Class Current: 514/218
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• CPC Class Codes: A61K 31/4025 not condensed and containing further heterocyclic rings, e.g. cromakalim
• CPC Class Codes: A61K 31/403 condensed with carbocyclic rings, e.g. carbazole
• CPC Class Codes: A61K 31/416 condensed with carbocyclic ring systems, e.g. indazole
• 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 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/53 having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine melarsoprol A61K31/555 ; with four nitrogen atoms A61K31/495
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system

Abstract

A method for treating Attention Deficit/Hyperactivity Disorder (ADHD) in humans using a 5-HT_1A receptor agonist is provided.

Claims

1. A method of treating Attention-Deficit/Hyperactivity Disorder (“

ADHD”

) in humans by administering a pharmaceutical formulation containing a therapeutically effective amount of a compound or compounds having full agonist or partial agonist activity at 5-HT_1A receptors, wherein any non-5-HT_1A agonist that is included in said formulation as an active ingredient, no such active ingredient is nicotine or a nicotinic agonist with the proviso that said formulation does not comprise nicotine or a nicotine agonist or buspirone or sunipetron.

2. A method according to claim 1 wherein 5-HT_1A agonist is a compound according to the formula I:

3. The method of claim 2,

wherein

R₁, R₂, and R₆ are hydrogen;

R₃, is a lipophilic aromatic alkyl, selected from the group consisting of benzene, halogenated benzene, cyclohexane, and 2-thiophene;

X is O, S, or NH;

B is the group —

CH₂—

CH₂—

n has the value 1; and

p has the value 0 or 1,

and where p has the value 1,

A is O—

CH₃, or forms, with the two carbon atoms of the phenyl group, an optionally substituted benzodioxane, a hydroxyalkyl having 1-2 carbon atoms, or a furan, R₃,

and where A is not O—

CH₃,

 

R₄ is hydrogen, and

 

R₅ is hydrogen, or chiral —

CH₂OH—

at the 2 position of the benzodioxane ring.

4. The method according to claim 3, w % herein the compound is flesinoxan, wherein

R₁, R₂, and R₆ are hydrogen;

R₃, is halogenated benzene group, having a fluoro in the para position;

X is O;

B is the group —

CH₂—

CH₂—

;

n has the value 1;

p has the value 1;

A is benzodioxane;

R₄ is hydrogen

R₅ is chiral —

CH₂OH—

at the 2 position of the benzodioxane ring; and

the salt is hydrochloride.

5. The method according to claim 4, wherein the compound is administered at a dose of approximately 0.04 mg/day to 4 mg/day.

6. The method according to claim 5, wherein the compound is administered at a dose of approximately 0.1 mg/day and 1 mg/day.

7. The method according to claim 6, wherein the compound is administered at a dose of approximately 0.1 mg/day and 0.5 mg/day.

8. The method according to claim 1, wherein the 5-HT_1A agonist is a compound having the formula II:

9. The method according to claim 8, wherein the compound is lesopitron,

wherein

n is 4,

R is chloro;

and

the salt is dihydrochloride.

10. The method according to claim 1, wherein the 5-HT_1A agonist is selected from the group consisting of flesinoxan, lesopitron, BAY x 3702, F11440, LY228729, LY293284, NAE-086, S14506, S14671, S16924, or gepirone.

11. The method according to claim 1, wherein the 5-HT_1A agonist(s) is the sole ADHD active component(s) of the formulation.

12. The method according to claim 10, wherein the 5-HT_1A agonist is administered at a dose of approximately 0.01 mg/day to 100 mg/day.

13. The method according to claim 10, wherein the 5-HT_1A agonist is administered at a dose of approximately 0.1 mg/day and 10 mg/day.

14. The method according to claim 10, wherein the 5-HT_1A agonist is administered at a dose of approximately 0.1 mg/day and 2 mg/day.

15. The method according to claim 1, wherein the intrinsic activity of the 5-HT_1A agonist is at least 0.5-1.0.

16. The method according to claim 15, wherein the intrinsic activity of the 5-HT_1A agonist is at least about 0.6-1.0.

17. The method according to claim 16, wherein the intrinsic activity of the 5-HT_1A agonist is at least about 0.7-1.0.

18. The method according to claim 17, wherein the intrinsic activity of the 5-HT_1A agonist is at least about 0.8-1.0.

19. The method according to claim 2, wherein the difference in affinity of the 5-HT_1A agonist for 5-HT_1A receptors compared to any of 5-HT_1B/1D, 5-HT₂, D₂, D₄, α

₁ or α

₂ receptors or SERT, DAT, or NET (Δ

pK_i) is at least 1.

20. The method according to claim 2, wherein the difference in affinity of the 5-HT_1A agonist for 5-HT_1A compared to D₂ receptors (Δ

pK_i) is at least about 2.

21. The method according to claim 2, wherein the difference in affinity of the 5-HT_1A agonist for 5-HT_1A receptors compared to any of 5-HT_1B/1D, 5-HT₂, D₂, D₄, α

₁ or α

₂ receptors or SERT, DAT, or NET (Δ

pK_i) is at least about 2.