Methods and Compositions Using Cholinesterase Inhibitors

• US 20110053981A1
• Filed: 10/12/2010
• Published: 03/03/2011
• Est. Priority Date: 05/17/2002
• Status: Abandoned Application

• Current Assignee: Eisai R & D Management Company Limited (Eisai Medical Research Incorporated)
• Original Assignee: Eisai R & D Management Company Limited (Eisai Medical Research Incorporated)
• Inventors: Ieni, John, Pratt, Raymond
• Application Number:
  US12/902,534
• Publication Number:
  US 20110053981A1
• Time in Patent Office: Days
• US Class Current: 514/319
• 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 31/13 Amines A61K31/04 takes precedence
• CPC Class Codes: A61K 31/15 Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) ; Imines (C—N=C)
• 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 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61K 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

The invention provides methods for treating and/or preventing Alzheimer'"'"'s disease, psychiatric illnesses, encephalitis, meningitis, fetal alcohol syndrome, Karsakoff'"'"'s syndrome, anoxic brain injury, cardiopulmonary resuscitation injuries, diabetes, Sjogren'"'"'s syndrome, mental retardation, developmental delay, menopause, strokes, macular degeneration, neuronal loss associated with macular degeneration, sleep disorders, severe Alzheimer'"'"'s disease, jet lag, post-traumatic stress disorder, anxiety disorders, panic attacks, obsessive-compulsive disorder, amnesia, and other disorders by administering to a patient in need thereof at least one cholinesterase inhibitor. The invention also provides novel pharmaceutical compositions that can be administered to the eyes or to the nose of patients. In one embodiment, the cholinesterase inhibitor is donepezil, a stereoisomer thereof and/or a pharmaceutically acceptable salt thereof. In other embodiments, the cholinesterase inhibitor can be one or more of phenserine, tolserine, phenethylnorcymserine, ganstigmine, epastigmine, tacrine, physostigmine, pyridostigmine, neostigmine, rivastigmine, galantamine, citicoline, velnacrine, huperzine, metrifonate, heptastigmine, edrophonium, TAK-147, T-82, and upreazine.

Claims

1-23. -23. (canceled)

24. A method for treating Alzheimer'"'"'s disease, Parkinson'"'"'s disease, or vascular dementia in a patient in need thereof comprising administering a therapeutically effective amount of at least one cholinesterase inhibitor and at least one NMDA receptor blocker.

25. The method of claim 24, wherein the cholinesterase inhibitor is donepezil and/or a pharmaceutically acceptable salt thereof.

26. The method of claim 24, wherein the cholinesterase inhibitor is a compound of formula I, a stereoisomer thereof, and/or a pharmaceutically acceptable salt thereof:

27. The method of claim 24, wherein the cholinesterase inhibitor is a compound of formula II, a stereoisomer thereof, and/or a pharmaceutically acceptable salt thereof:

28. The method of claim 24, wherein the cholinesterase inhibitor is a compound of formula III, a stereoisomer thereof, and/or a pharmaceutically acceptable salt thereof:

29. The method of claim 24, wherein the cholinesterase inhibitor is 1-benzyl-4-((5,6-dimethoxy-1-indanon)-2-yl)methylpiperidine;

1-benzyl-4-((5,6-dimethoxy-1-indanon)-2-ylidenyl)methylpiperidine;

1-benzyl-4-((5-methoxy-1-indanon)-2-yl)methylpiperidine;

1-benzyl-4-((5,6-diethoxy-1-indanon)-2-yl)methylpiperidine;

1-benzyl-4-((5,6-methnylenedioxy-1-indanon)-2-yl)methylpiperidine;

1-(m-nitrobenzyl)-4-((5,6-dimethoxy-1-indanon)-2-yl)methylpiperidine;

1-cyclohexylmethyl-4-((5,6-dimethoxy-1-indanon)-2-yl)methylpiperidine;

1-(m-fluorobenzyl)-4-((5,6-dimethoxy-1-indanon)-2-yl)methylpiperidine;

1-benzyl-4-((5,6-dimethoxy-1-indanon)-2-yl)propylpiperidine;

1-benzyl-4-((5-isopropoxy-6-methoxy-1-indanon)-2-yl)methylpiperidine;

1-benzyl-4-((5,6-dimethoxy-1-oxoindanon)-2-yl)propenylpiperidine;

or a stereoisomer and/or a pharmaceutically acceptable salt thereof.

30. The method of claim 24, wherein the cholinesterase inhibitor is a compound of formula IV or a pharmaceutically acceptable salt thereof:

31. The method of claim 24, wherein the cholinesterase inhibitor is

32. The method of claim 24, wherein the cholinesterase inhibitor is a compound of formula VI or a pharmaceutically acceptable salt thereof:

33. The method of claim 24, wherein the cholinesterase inhibitor is a compound of formula VII or a pharmaceutically acceptable salt thereof:

34. The method of claim 24, wherein the NMDA receptor blocker is memantine and/or a pharmaceutically acceptable salt thereof.

35. The method of any one of claims 24 to 34, wherein the pharmaceutically acceptable salt is a hydrochloride salt.