CO-ADMINISTRATION OF PIMAVANSERIN WITH OTHER AGENTS

• US 20140349976A1
• Filed: 05/28/2014
• Published: 11/27/2014
• Est. Priority Date: 09/21/2007
• Status: Abandoned Application

• Current Assignee: Acadia Pharmaceuticals Inc.
• Original Assignee: Acadia Pharmaceuticals Inc.
• Inventors: HACKSELL, Uli, MCFARLAND, Krista
• Application Number:
  US14/289,450
• Publication Number:
  US 20140349976A1
• Time in Patent Office: Days
• US Class Current: 514/129
• CPC Class Codes: A61K 31/4465 only substituted in position 4
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/473 ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
• 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 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• 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
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 25/32 Alcohol-abuse
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

As disclosed herein, co-administration of pimavanserin with an agent that ameliorates one or more cholinergic abnormalities can have a synergistic effect on the efficacy of the agent. Disclosed herein are compositions which include pimavanserin in combination with an agent that ameliorates one or more cholinergic abnormalities. Also disclosed herein are methods for ameliorating or treating a disease condition characterized by one or more cholinergic abnormalities that can include administering pimavanserin in combination with an agent that ameliorates one or more cholinergic abnormalities.

Claims

1-32. -32. (canceled)

33. A method for ameliorating or treating a disease condition characterized by one or more cholinergic abnormalities, comprising administering to a subject with the disease condition:

(a) pimavanserin, or a pharmaceutically acceptable salt thereof; and

(b) a cholinesterase inhibitor, wherein the cholinesterase inhibitor is metrifonate, physostigmine, neostigmine, pyridostigmine, demarcarium, rivastigmine, aldicarb, bendiocarb, bufencarb, carbaryl, carbendazim, carbetamide, carbofuran, chlorbufam, chloropropham, ethiofencarb, formetanate, methiocarb, methomyl, oxamyl, phenmedipham, pinmicarb, pirimcarb, propamocarb, propham, propoxus, donepezil, tacrine, edrophonium, echothiophate, diisopropyl fluorophosphate, dimebon, Huperzine A, ((2-[2-(1-benzylpiperidin-4-yl)ethyl]-2,3-dihydro-9-methoxy-1H-pyrrolo[3,4-b]quinolin-1-one hemifumarate)), zanapezil, phenserine, quilostigmine, ganstigmine, butyrophenones, imipramines, tropates, phencyclidines, curariforms, ethephon, ethopropazine, iso-OMPA, tetrahydrofurobenzofuran cymserine, N¹-phenethyl-norcymserine, N⁸-benzylnorcymserine, N¹,N⁸-bisnorcymserine, N¹—

N⁸-bisbenzylnorphysostigmine, N¹,N⁸-bisbenzylnorphenserine, or N¹,N⁸-bisbenzylnorcymserine.

34. The method of claim 33, wherein the cholinesterase inhibitor is metrifonate, pyridostigmine, rivastigmine, bufencarb, carbaryl, carbofuran, chlorbufam, chloropropham, ethiofencarb, formetanate, methomyl, oxamyl, pinmicarb, donepezil, tacrine, edrophonium, diisopropyl fluorophosphate, dimebon, zanapezil, phenserine, quilostigmine, phencyclidines, curariforms, ethopropazine, tetrahydrofurobenzofuran cymserine, N¹-phenethyl-norcymserine, N⁸-benzylnorcymserine, or N¹,N⁸-bisnorcymserine.

35. The method of claim 33, wherein the cholinesterase inhibitor is metrifonate, rivastigmine, dimebon, phencyclidines, diisopropyl fluorophosphate, or donepezil.

36. The method of claim 33, wherein the cholinesterase inhibitor is metrifonate.

37. The method of claim 33, wherein the cholinesterase inhibitor is rivastigmine.

38. The method of claim 33, wherein the cholinesterase inhibitor is dimebon.

39. The method of claim 33, wherein the cholinesterase inhibitor is diisopropyl fluorophosphate.

40. The method of claim 33, wherein the cholinesterase inhibitor is donepezil.

41. The method of claim 33, wherein a pharmaceutically acceptable salt of pimavanserin is administered, wherein the pharmaceutically acceptable salt is a tartrate or a hemi-tartrate salt.

42. The method of claim 41, wherein the pharmaceutically acceptable salt of pimavanserin is a crystalline Form C tartrate salt.

43. The method of claim 33, wherein the amount of pimavanserin, or a pharmaceutically acceptable salt thereof, is from about 0.1 mg to about 500 mg per day.

44. The method of claim 33, wherein the amount of pimavanserin, or a pharmaceutically acceptable salt thereof, is from about 1 mg to about 250 mg per day.

45. The method of claim 33, wherein the amount of pimavanserin, or a pharmaceutically acceptable salt thereof, is about 1 mg to about 40 mg per day.

46. The method of claim 33, wherein the amount of pimavanserin, or a pharmaceutically acceptable salt thereof, is about 10 mg per day.

47. The method of claim 33, wherein the amount of pimavanserin, or a pharmaceutically acceptable salt thereof, is about 20 mg per day.

48. The method of claim 33, wherein the amount of pimavanserin, or a pharmaceutically acceptable salt thereof, is about 40 mg per day.

49. The method of claim 33, wherein pimavanserin is administered orally, parenterally, or intravenously.

50. The method of claim 49, wherein pimavanserin is administered orally.

51. The method of claim 50, wherein pimavanserin is administered as one or more tablets.