5-ht4 receptor agonist compounds for treatment of cognitive disorders

Abstract

The invention provides methods for the treatment of cognitive disorders utilizing specific 5-HT 4 receptor agonist compounds, in particular, methods utilizing these compounds in combination with other agents, specifically acetylcholinesterase inhibitors, for the treatment of Alzheimer's disease and other cognitive disorders.

1 - 13 . (canceled) 
     
     
         14 . A pharmaceutical composition comprising an acetylcholinesterase inhibitor, a 5-HT 4  receptor agonist compound wherein the compound is selected from 1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid {(1S,3R,5R)-8-[(R)-2-hydroxy-3-(methanesulfonyl-methyl-amino)propyl]-8-azabicyclo[3.2.1]oct-3-yl}amide and 4-(4-{[(2-isopropyl-1H-benzoimidazole-4-carbonyl)amino]methyl}-piperidin-1-ylmethyl)piperidine-1-carboxylic acid methyl ester, and pharmaceutically acceptable salts thereof, and a pharmaceutically-acceptable carrier. 
     
     
         15 . The pharmaceutical composition of  claim 14  wherein the acetylcholinesterase inhibitor is donepezil hydrochloride. 
     
     
         16 . The pharmaceutical composition of  claim 14  wherein the 5-HT 4  receptor agonist compound is 1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid {(1S,3R,5R)-8-[(R)-2-hydroxy-3-(methanesulfonyl-methyl-amino)propyl]-8-azabicyclo[3.2.1]oct-3-yl}amide, or a pharmaceutically-acceptable salt thereof. 
     
     
         17 . The pharmaceutical composition of  claim 14  wherein the 5-HT 4  receptor agonist compound is 1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid {(1S,3R,5R)-8-[(R)-2-hydroxy-3-(methanesulfonyl-methyl-amino)propyl]-8-azabicyclo[3.2.1]oct-3-yl}amide hydrochloride. 
     
     
         18 . The pharmaceutical composition of  claim 14  wherein the 5-HT 4  receptor agonist compound is 4-(4-{[(2-isopropyl-1H-benzoimidazole-4-carbonyl)amino]methyl}-piperidin-1-ylmethyl)piperidine-1-carboxylic acid methyl ester. 
     
     
         19 - 20 . (canceled)