# US 2014/0155429 A1 · Treatment of Cognitive Disorders with Certain Alpha-7 Nicotinic Acid Receptor Agonists in Combination with Nicotine > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0155429 A1 - Document ID: US20140155429A1 - Status: Published application - Kind: A1 - Application number: 14/116,016 - Filed: 2012-05-08 - Published: 2014-06-05 - Earliest claimed: 2011-05-09 - Assignees: EnVivo Pharmaceuticals, Inc. - Applicants: EnVivo Pharmaceuticals, Inc. - Inventors: Gerhard Koenig - Web page: https://patentgrep.com/patent/US20140155429A1 ## CPC - C07D 453/02: containing not further condensed quinuclidine ring systems - A61K 31/439: the ring forming part of a bridged ring system, e.g. quinuclidine (8-azabicyclo [3.2.1] octanes A61K31/46) - A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) - A61K 31/465: Nicotine; Derivatives thereof - A61P 25/00: Drugs for disorders of the nervous system - 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 - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract A method for improving cognition comprising co-administering to a subject an alpha 7 agonist, or a pharmaceutically acceptable salt thereof and a tobacco-free nicotine dosage is described together with related compositions. ## Claims ### Claim 1 A method for improving cognition and/or treating a cognitive disorder comprising co-administering to a subject a therapeutically effective amount of (1) a tobacco-free nicotine dosage; and (2) a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R1 is 1-azabicyclo[2.2.2]oct-3-yl, R2 is hydrogen or (C1-C6)alkyl, R3 is hydrogen, halogen or (C1-C6)alkyl, A is oxygen or sulfur, and Z is halogen, formyl, carbamoyl, cyano, trifluoromethyl, trifluoromethoxy, nitro, amino, formamido, acetamido, (C1-C6)alkyl, (C1-C6)alkyoxy, (C1-C6)alkylthio, (C1-C6)alkylamino, heteroaryl-carbonylamino, arylcarbonylamino, (C1-C4)alkylsulfonylamino, di(arylsulfonyl)amino, (C3-C6)cycloalkylcarbonylmethyl or amino(hydroxyimino)methyl. ### Claim 2 (depends on 1) The method according to claim 1 wherein R2 is hydrogen, R3 is hydrogen, A is sulfur, and Z is halogen, formyl, carbamoyl, cyano, trifluoromethyl, trifluoromethoxy, nitro, amino, formamido, acetamido, (C1-C6)alkyl, (C1-C6)alkyoxy, (C1-C6)alkylthio, or (C1-C6)alkylamino. ### Claim 3 (depends on 1) The method according to claim 1 wherein Z is heteroaryl-carbonylamino, arylcarbonylamino, (C1-C4)alkylsulfonylamino, di(arylsulfonyl)amino, (C3-C6)cycloalkylcarbonylmethyl or amino(hydroxyimino). ### Claim 4 (depends on 1) The method according to claim 1 wherein Z is halogen, cyano, trifluoromethyl, trifluoromethoxy, methyl, ethyl, methoxy, or ethoxy. ### Claim 5 (depends on 1) The method according to claim 1 wherein the compound of formula (I) is (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide. ### Claim 6 (depends on 1) The method of claim 1 wherein the subject has been diagnosed with Alzheimer's disease or pre-Alzheimer's disease. ### Claim 7 (depends on 1) The method of claim 1 wherein the subject has been diagnosed with mild to moderate Alzheimer's disease. ### Claim 8 (depends on 1) The method of claim 1 wherein the subject has been diagnosed with moderate to severe Alzheimer's disease. ### Claim 9 (depends on 1) The method of claim 1 wherein the subject has been diagnosed with schizophrenia or schizoaffective disorder. ### Claim 10 (depends on 1) The method of claim 1, wherein the method improves one or more of: learning, delayed memory, attention, working memory, visual learning, speed of processing, vigilance, verbal learning, visual motor function, social cognition, long term memory or executive function. ### Claim 11 (depends on 1) The method of claim 1 wherein the (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide is administered at a dose that is therapeutically effective in the absence of a tobacco-free nicotine dosage. ### Claim 12 (depends on 1) The method of claim 1 wherein one or both of the (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide and a tobacco-free nicotine dosage is administered at a subclinical dose. ### Claim 13 (depends on 1) The method of claim 1 wherein (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof is administered at 0.03 to 1.0 mg/day. ### Claim 14 (depends on 1) The method of claim 1 wherein (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof is orally administered at 0.03 to 0.5 mg/day. ### Claim 15 (depends on 1) The method of claim 1 wherein (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof is orally administered at 0.03 to 0.3 mg/day. ### Claim 16 (depends on 1) The method of claim 1 wherein (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof is orally administered at 0.03 to 0.1 mg/day. ### Claim 17 A pharmaceutical composition comprising (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof and a tobacco-free nicotine dosage (TFN). ### Claim 18 A daily unit dosage pharmaceutical composition comprising 0.03 to 1.0 mg of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof, a TFN, and a pharmaceutically acceptable carrier. ### Claim 19 (depends on 18) The daily unit dosage pharmaceutical composition of claim 18 comprising 0.03 to 0.5 mg of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof. ### Claim 20 (depends on 18) The daily unit dosage pharmaceutical composition of claim 18 comprising 0.03 to 0.3 mg of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof. ### Claim 21 (depends on 18) The pharmaceutical composition of claim 18 comprising 0.03 to 0.1 mg of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof. ### Claim 22 A packaged pharmaceutical comprising a package containing a unit dosage pharmaceutical composition comprising (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a transdermal patch comprising a tobacco-free nicotine dosage.