Pharmaceutical composition and method for treating disorders of the central nervous system
Disorders of the ventral nervous system (CNS) are treated by the administration of a GABA analog such as gabapentin or pregablin, an NMDA receptor antagonist such as dextromethorphan or d-methodone and, optionally, another pharmacologically active substance, e.g., one which is effective for the treatment of a CNS disorder.
1 . A pharmaceutical composition comprising:
(a) at least one GABA analog and
(b) at least one nontoxic antagonist for the NMDA receptor,
the combined amount of (a) and (b) in the composition being a CNS disorder-treating amount and the amount of (b) in the composition being sufficient to potentiate the CNS disorder-treating effectiveness of (a).
2 . The composition of claim 1 wherein the GABA analog possesses the structure
wherein R 1 is hydrogen or lower alkyl and n is an integer of from 4 to 6, and the pharmaceutically acceptable salts thereof.
3 . The composition of claim 1 wherein the GABA analog is gabapentin.
4 . The composition of claim 1 wherein the GABA analog possesses the structure
wherein R 1 is a straight or branched alkyl of from 1 to 6 carbon atoms, phenyl, or cycloalkyl of from 3 to 6 atoms, R 2 is hydrogen or methyl and R 3 is hydrogen, methyl, or carboxyl, and the pharmaceutically acceptable salts, diasteromers and enantiomers thereof.
5 . The composition of claim 1 wherein the GABA analog is pregabalin.
6 . The composition of claim 1 wherein the nontoxic NMDA receptor antagonist is at least one member selected from the group consisting of dextromethorphan, dextrorphan, amantadine, memantine, d-methadone and pharmaceutically acceptable salts thereof.
7 - 10 . (canceled)
11 . The composition of claim 1 wherein (a) and (b) of the pharmaceutical composition is present in a combined sustained release carrier.
12 . The composition of claim 1 wherein (a) and (b) of the pharmaceutical composition are present in separate sustained release carriers.
13 . The composition of claim 1 wherein the pharmaceutical composition contains a therapeutically effective amount of at least one other pharmacologically active substance (c).
14 . The composition of claim 1 wherein the pharmaceutical composition contains a therapeutically effective amount of at least one other pharmacologically active substance (c) which is a drug for treating a CNS disorder.
15 . The composition of claim 1 wherein the pharmaceutical composition contains a therapeutically effective amount of at least one other pharmaceutically active substance (c) which is a drug or drug combination for the treatment of a CNS disorder selected from the group consisting of nicotine, nicotinic compounds, tacrine, donezepil, carbidopa in combination with levodopa, selegiline, bromocriptine, haloperidol, clonidine, pimozide, fluphenazine, benzodiazepines, clonazepam, clorpromazine, fluoxetine, clomipramine, amitriptyline, nortriptyline, imipramine, buspirone, bupropion hydrochloride, venlafaxine, milnacipran, duloxetine, mirtazapine, nefazodone, paroxetine, sertraline, riluzole, trazodone, doxepin and methylphenidate.
16 . The composition of claim 1 wherein the CNS disorder is classified in the International Classification of Diseases of the World Health Organization.
17 . The composition of claim 1 wherein the CNS disorder is presenile dementia, senile dementia, movement disorder, hyperkinesias, mania, attention deficit disorder, depression, anxiety, obsessive-compulsive disorder, dyslexia, schizophrenia, headache disorder, epilepsy, Tourette's syndrome or Asperger's syndrome.
18 - 31 . (canceled)
32 . A pharmaceutical composition comprising: (a) at least one GABA analog in an extended release form in combination with (b) at least one nontoxic antagonist for the NMDA receptor in an immediate release form, the combined amount of (a) and (b) in the composition being a CNS disorder-treating amount and the amount of (b) in the composition being sufficient to potentiate the CNS disorder-treating effectiveness of (a).
33 . The composition of claim 32 wherein the GABA analog possesses the structure
wherein R 1 is hydrogen or lower alkyl and n is an integer of from 4 to 6, and the pharmaceutically acceptable salts thereof.
34 . The composition of claim 32 wherein the GABA analog is gabapentin.
35 . The composition of claim 32 wherein the GABA analog possesses the structure
wherein R 1 is a straight or branched alkyl of from 1 to 6 carbon atoms, phenyl, or cycloaklyl of from 3 to 6 carbon atoms, R 2 is hydrogen or methyl and R 3 is hydrogen, methyl, or carboxyl, and the pharmaceutically acceptable salts, diastereomers and enantiomers thereof.
36 . The composition of claim 32 wherein the GABA analog is pregabalin.
37 . The composition of claim 32 wherein the nontoxic NMDA receptor antagonist is at least one member selected from the group consisting of dextromethorphan, dextrorphan, amantadine, memantine, d-methadone and pharmaceutically acceptable salts thereof.
38 - 41 . (canceled)
42 . The composition of claim 32 wherein the at least one nontoxic NMDA receptor antagonist is present in an immediate release carrier.
43 . The composition of claim 32 wherein the extended release form is an extended release carrier comprising abase material selected from the group consisting of a hydrophilic polymer, a hydrophobic polymer, a long chain hydrocarbon, a polyalkylene glycol, higher aliphatic alcohols, acrylic resins, and mixtures thereof.
44 . The composition of claim 43 wherein the at least one nontoxic NMDA receptor antagonist is applied to the extended release carrier's exterior surface.
45 . The composition of claim 32 wherein the extended release form comprises a base material having a coating that controls the release of the GABA analog.
46 . The composition of claim 45 wherein the coating includes the at least one nontoxic NMDA receptor antagonist.
47 . The composition of claim 32 wherein the pharmaceutical composition contains a therapeutically effective amount of (c) at least one other pharmacologically active substance.
48 . The composition of claim 47 wherein the pharmacologically active substance (c) is included in the extended release form.
49 . The composition of claim 47 wherein the pharmacologically active substance (c) is included in the immediate release form.
50 . The composition of claim 47 wherein the pharmacologically active substance (c) is included in both the extended release form and the immediate release form.
51 . The composition of claim 32 wherein the pharmaceutical composition contains a therapeutically effective amount of at least one other pharmacologically active substance (c) which is a drug for treating a CNS disorder.
52 . The composition of claim 32 wherein the pharmaceutical composition contains a therapeutically effective amount of at least one other pharmaceutically active substance (c) which is a drug or drug combination for the treatment of a CNS disorder selected from the group consisting of nicotine, nicotinic compounds, tacrine, donezepil, carbidopa in combination with levodopa, selegiline, bromocriptine, haloperidol, clonidine, pimozide, fluphenazine, benzodiazepines, clonazepam, clorpromazine, fluoxetine, clomipramine, amitriptyline, nortriptyline, imipramine, buspirone, bupropion hydrochloride, venlafaxine, milnacipran, duloxetine, mirtazapine, nefazodone, paroxetine, sertraline, riluzole, trazodone, doxepin and methylphenidate.
53 . The composition of claim 32 wherein the CNS disorder is classified in the International Classification of Diseases of the World Health Organization.
54 . The composition of claim 32 wherein the CNS disorder is presenile dementia, senile dementia, movement disorder, hyperkinesias, mania, attention deficit disorder, depression, anxiety, obsessive-compulsive disorder, dyslexia, schizophrenia, headache disorder, epilepsy, Tourette's syndrome or Asperger's syndrome.
55 . A method of treating a CNS disorder which comprises administering to a mammal in need of treatment for a CNS disorder A CNS disorder treating amount of pharmaceutical composition comprising:
(a) at least one GABA analog and
(b) at least one nontoxic antagonist for the NMDA receptor,
the combined amount of (a) and (b) in the composition being a CNS disorder-treating amount and the amount of (b) in the composition being sufficient to potentiate the CNS disorder-treating effectiveness of (a).
56 . A method of treating a CNS disorder which comprises administering to a mammal in need of treatment for a CNS disorder A CNS disorder treating amount of pharmaceutical composition comprising: (a) at least one GABA analog in an extended release form in combination with (b) at least one nontoxic antagonist for the NMDA receptor in an immediate release form, the combined amount of (a) and (b) in the composition being a CNS disorder-treating amount and the amount of (b) in the composition being sufficient to potentiate the CNS disorder-treating effectiveness of (a).