Use of anti-connexin agents for enhancing the therapeutic effect of acetylcholinesterase inhibitors

Abstract

This invention relates to improvements in therapeutic neurological and neuropsychic treatments using acetylcholinesterase inhibitors. More specifically, the invention enables the effects of the reversible acetylcholinesterase inhibitor donepezil to be potentiated by certain molecules, referred to here as connexin-blocking agents. Said connexin-blocking agent is preferably meclofenamic acid.

1 . Therapeutic substance combination product containing at least one connexin-blocking agent and one acetylcholinesterase inhibitor (AChEI),
 wherein said connexin-blocking agent is meclofenamic acid and   said acetylcholinesterase inhibitor (AChEI) is donepezil or a pharmaceutical salt thereof.   
     
     
         2 . The combination product according to  claim 1 , containing between 0.5 μg/kg/day and 0.5 mg/kg/day of meclofenamic acid. 
     
     
         3 . The combination product according to  claim 1 , containing between 1 μg/kg/day and 1 mg/kg/day of donepezil or a pharmaceutical salt thereof. 
     
     
         4 . Method of treating cognitive disorders, which comprises administering to a patient in need there of an effective amount of a therapeutic substance combination product containing at least one connexin-blocking agent and an acetylcholinesterase inhibitor (AChEI),
 wherein said connexin-blocking agent is meclofenamic acid and   said acetylcholinesterase inhibitor (AChEI) is donepezil or a pharmaceutical salt thereof, and wherein said connexin-blocking agent and said acetylcholinesterase are administered simultaneously, separately or sequentially.   
     
     
         5 . The method according to  claim 4 , wherein said cognitive disorder is chosen from Alzheimer's disease, Parkinson disease, vascular dementia and senile dementia. 
     
     
         6 . The method according to  claim 4 , wherein the therapeutic substance combination product contains between 0.5 μg/kg/day and 0.5 mg/kg/day of meclofenamic acid. 
     
     
         7 . The method according to  claim 4 , wherein the therapeutic substance combination product contains between 1 μg/kg/day and 1 mg/kg/day of donepezil or a pharmaceutical salt thereof. 
     
     
         8 . Method of potentiating the effect of donepezil or a pharmaceutical salt thereof in patients suffering from cognitive disorders, which comprises administering to said patient a connexin-blocking agent
 wherein said connexin-blocking agent is meclofenamic acid.   
     
     
         9 . The method according to  claim 8 , wherein said cognitive disorder is chosen from Alzheimer's disease, Parkinson disease, vascular dementia and senile dementia. 
     
     
         10 . The method according to  claim 8 , wherein the meclofenamic acid is used at a dose between 0.5 μg/kg/day and 0.5 mg/kg/day. 
     
     
         11 . The method according to  claim 8 , wherein the donepezil or a salt thereof is used at a dose between 1 μg/kg/day and 1 mg/kg/day. 
     
     
         12 . The combination product according to  claim 2 , containing between 1 μg/kg/day and 1 mg/kg/day of donepezil or a pharmaceutical salt thereof. 
     
     
         13 . The method according to  claim 5 , wherein the therapeutic substance combination product contains between 0.5 μg/kg/day and 0.5 mg/kg/day of meclofenamic acid. 
     
     
         14 . The method according to  claim 5 , wherein the therapeutic substance combination product contains between 1 μg/kg/day and 1 mg/kg/day of donepezil or a pharmaceutical salt thereof. 
     
     
         15 . The method according to  claim 6 , wherein the therapeutic substance combination product contains between 1 μg/kg/day and 1 mg/kg/day of donepezil or a pharmaceutical salt thereof. 
     
     
         16 . The method according to  claim 9 , wherein meclofenamic acid is used at a dose between 0.5 μg/kg/day and 0.5 mg/kg/day. 
     
     
         17 . The method according to  claim 9 , wherein donepezil or a salt thereof is used at a dose between 1 μg/kg/day and 1 mg/kg/day. 
     
     
         18 . The method according to  claim 10 , wherein donepezil or a salt thereof is used at a dose between 1 μg/kg/day and 1 mg/kg/day.