Pharmacological treatment of cognitive impairment

Abstract

Methods for treating an individual to improve cognitive function are provided. In the subject methods, an effective amount of a noncompetitive GABAA ionophore blocker is administered to the individual, resulting in an improvement in cognitive function of the host. The subject methods find use in a variety of different applications.

What is claimed is: 
     
         1 . A method of improving a cognitive function of child or young adult mammal suffering from mental retardation, said method comprising:
 administering not more than once daily to the child or young adult an effective amount of a pharmaceutical formulation comprising a GABA A  receptor chloride ionophore blocker;   wherein cognitive function of the child or young adult is improved.   
     
     
         2 . The method of  claim 1 , wherein the effective dose is less than 0.1× the kindling dose and is effective to transiently alter the chloride influx at GABA A  receptors in the central nervous system. 
     
     
         3 . The method of  claim 1 , wherein the GABA A  receptor chloride ionophore blocker is a noncompetitive antagonist. 
     
     
         4 . The method of  claim 1 , wherein the GABA A  receptor chloride ionophore blocker is administered orally. 
     
     
         5 . The method of  claim 1 , wherein the GABA A  receptor chloride ionophore blocker is metrazol. 
     
     
         6 . The method of  claim 5 , wherein the metrazol is administered at a dose of 0.1 to 3 mg/kg body weight of the child or young adult. 
     
     
         7 . The method of  claim 6 , wherein the metrazol is administered once daily. 
     
     
         8 . The method of  claim 1 , wherein said GABA A  receptor chloride ionophore blocker is delivered parenterally. 
     
     
         9 . The method of  claim 8 , wherein said GABA A  receptor chloride ionophore blocker is chosen from bilobalide, ginkgolide B and picrotoxin. 
     
     
         10 . The method of  claim 1 , wherein the GABA A  receptor chloride ionophore blocker is administered daily for a period of at least about two weeks. 
     
     
         11 . The method of  claim 10 , wherein said cognitive function is at least one of learning and memory. 
     
     
         12 . The method of  claim 10 , further comprising the step of testing the child or young adult for improvement in at least one of learning and memory. 
     
     
         13 . The method of  claim 1 , wherein the young adult or child is human. 
     
     
         14 . A method of improving a cognitive function of an individual with Down Syndrome, the method comprising:
 administering not more than once daily to the individual an effective amount of a pharmaceutical formulation comprising a GABA A  receptor chloride ionophore blocker;   wherein cognitive function of the individual is improved.   
     
     
         15 . The method of  claim 14 , wherein the effective dose is less than 0.1× the kindling dose and is effective to transiently alter the chloride influx at GABA A  receptors in the central nervous system. 
     
     
         16 . A kit for use in improving a cognitive function of an individual mammal suffering from mental retardation, said kit comprising:
 GABA A  receptor chloride ionophore blocker in a non-epileptic dose, in a pharmaceutically acceptable vehicle.   
     
     
         17 . The kit according to  claim 16 , wherein said kit further comprises instructions for treating said mental retardation. 
     
     
         18 . A method of screening a candidate agent for treatment of cognitive impairment associated with mental retardation, the method comprising:
 contacting a GABA A  receptor with a candidate agent;   determining if said agent is an ionophore blocker;   administering said agent to an animal in a model for mental retardation;   determining if said agent improve cognitive function.