Composition and Method for Treatment of Depression and Psychosis in Humans

• US 20140018348A1
• Filed: 07/07/2013
• Published: 01/16/2014
• Est. Priority Date: 07/12/2012
• Status: Active Grant

• Current Assignee: Glytech, LLC
• Original Assignee: Glytech, LLC
• Inventors: Javitt, Daniel C.
• Granted Patent: US 9,737,531 B2
• Time in Patent Office: Days
• US Class Current: 514/211.13
• 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 31/06 the aromatic ring being substituted by nitro groups
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 31/42 Oxazoles
• CPC Class Codes: A61K 31/431 containing further heterocyclic rings, e.g. ticarcillin, azlocillin, oxacillin
• CPC Class Codes: A61K 31/4525 containing a five-membered ring with oxygen as a ring hetero atom
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 31/553 having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
• CPC Class Codes: A61K 31/554 having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Compositions and methods tor the treatment of depression and psychoses in humans are disclosed. More particularly, the invention is directed to formulations containing antipsychotic and/or antidepressant medications and also containing an NMPAR antagonist. The present invention is also directed to methods for the treatment of humans suffering from depression and other psychoses, including, schizophrenia, by administration of the inventive compositions in antidepressant and/or antipsychotic effective amounts.

Claims

1. A composition for treating depression or psychosis in a human in need of such treatment comprising an antidepression or antipsychosis effective amount of an oral or parenteral dosage composed of a first compound selected from the group consisting of an antidepressants agent and an antipsychotic agent, which first compound includes a selective 5-HT2A receptor antagonist/inverse agonist and a second compound selected from the group consisting of a NMDAR receptor antagonists.

2. The composition of claim 1 wherein the NMDAR receptor antagonist is selected from the group consisting of non-selective antagonists, selective antagonists and combinations thereof.

3. The composition of claim 1 wherein the antipsychotic is selected from the group consisting of risperidone, olanzapine, quetiapine, aripiprazole, clozapine, iloperidone, sertindole, asenapine, lurasidone, and cariprazine.

4. The composition of claim 1 wherein the antidepressant is selected from the group consisting a tetracyclic antidepressant (TeCA), a selective serotonin reuptake inhibitor (SSRI), a serotonin/norephinephrine reuptake inhibitor (SNRI), a 5-HT2A antagonist or inverse agonist and combinations thereof.

5. The composition of claim 1 wherein the antidepressant is selected from the group consisting of imipramine, amitryptiline, desipramine, clomipramine, amoxapine, setiptiline, maprotiline, mianserin, mirtazapine, fluoxetine, fluvoxamine, paroxetine, citalopram, escitalopram, duloxetine, venlafaxine, dapoxetine, indalpine, and valzodone.

6. The composition of claim 1 wherein the selective 5-HT2A receptor antagonist/inverse agonist is selected from a group including MDL100,907, ritanserin, ketanserin, eplivanserin, CYR-101 and pimavanserin (ACP-103)

7. The composition of claim 1 wherein the NMDAR antagonist selected from the group consisting of antagonists of the glycine, glutamate and channel recognition sites.

8. The composition of claim 1 wherein the NMDAR antagonist is selective for NMDAR containing an NR2B subunit.

9. The composition of claim 1 wherein the NMDAR antagonist consists of D-cycloserine, administered at a dose of 500 mg/d or greater

10. The composition of claim 1 wherein the NMDAR antagonist is selected from the group consisting of CGS-19755, D-CPPene, MK-0657, AZD6765, Glyx-13, NRX-1059, or EVT-101

11. The composition of claim 1 is in the form of an oral or parenteral dosage.

12. A method for the treatment of depression or psychosis in a human subject comprising administering to the human an anti-depression or anti-psychosis effective amount of the composition of claim 1 orally, intramuscularly, intravenously, intraperitoneally, parentally or orally.

13. A method for the treatment of depression in a human subject comprising administering to the human an anti-depression effective amount of the composition of claim 1 in the form of an oral or parenteral dosage.

14. A method for the treatment of psychosis in a human subject comprising administering to the human an anti-psychosis effective amount of the composition of claim 1 in the form of an oral or parenteral dosage.

15. A method for the treatment of symptoms of autism psychosis in a human subject comprising administering to the human an anti-autism effective amount of the composition of claim 1 in the form of an oral or parenteral dosage.

16. A method for reducing the side effects associated with medications administered to a human subject for treatment of mental illness comprising administering a side-effect reducing effective amount of the composition of claim 1 in the form of an oral or parental dosage to the subject.

17. A pharmaceutical composition for the treatment of psychosis or depression comprising an anti-depression or anti-psychosis effective amount of an oral or parenteral dosage composed of a first compound selected from the group consisting of an antidepressants agent and an antipsychotic agent which compound includes a selective 5-HT2A receptor agonist/inverse antagonist and a second compound selected from the group consisting of a NMDAR receptor antagonist in the form of a sustained release dosage.