Compositions and methods for selective inhibition of nicotine acetylcholine receptors

Abstract

The present invention concerns methods for treating or preventing neurological disorders characterized by dysfunction of nicotinic acetylcholine receptors by administering 2,2,6,6-tetramethylpiperidin-4-yl heptanoate (TMPH), or a pharmaceutically acceptable salt thereof, to the patient. In another aspect, the present invention pertains to pharmaceutical compositions containing TMPH, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In another aspect, the present invention pertains to methods for selectively inhibiting nicotinic acetylcholine receptors that lack an α5, α6, or β3 subunit by contacting an effective amount of TMPH, or a pharmaceutically acceptable salt thereof, to the receptor. The method for selectively inhibiting nicotinic acethylcholine receptors that lack an α5 subunit can be carried out in vivo or in vitro.

1 . A compound having the structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . A composition comprising 2,2,6,6-tetramethylpiperidin-4-yl heptanoate, or a pharmaceutically acceptable salt thereof. 
     
     
         3 . The composition according to  claim 2 , wherein said composition further comprises a pharmaceutically acceptable carrier. 
     
     
         4 . A method for inhibiting a nicotinic acetylcholine receptor by contacting an effective amount of 2,2,6,6-tetramethylpiperidin-4-yl heptanoate, or a pharmaceutically acceptable salt thereof, to the receptor. 
     
     
         5 . The method of  claim 4 , wherein the nicotinic acetylcholine receptor lacks an alpha5 subunit, an alpha6 subunit, and a beta3 subunit. 
     
     
         6 . The method of  claim 4 , wherein the nicotinic acetylcholine receptor is a neuronal beta subunit-containing receptor lacking an alpha5 subunit, an alpha6 subunit, and a beta3 subunit. 
     
     
         7 . The method of  claim 4 , wherein the nicotinic acetylcholine receptor includes one or more of the following receptor subunits: alpha3, alpha4, beta2, beta4, and alpha7. 
     
     
         8 . The method of  claim 4 , wherein the nicotinic acetylcholine receptor includes two or more of the following receptor subunits: alpha3, alpha4, beta2, beta4, and alpha7. 
     
     
         9 . The method of  claim 4 , wherein the nicotinic acetylcholine receptor is selected from the group consisting of alpha4 beta2: alpha3 beta2; alpha3 beta4; and alpha7. 
     
     
         10 . The method of  claim 4 , wherein said contacting is carried out in vivo and comprises administering 2,2,6,6-tetramethylpiperidin-4-yl heptanoate, or a pharmaceutically acceptable salt thereof, to a patient. 
     
     
         11 . The method of  claim 10 , wherein the patient is a non-human mammal. 
     
     
         12 . The method of  claim 10 , wherein the patient is human. 
     
     
         13 . The method of  claim 10 , wherein said administering is by intravenous, oral, parenteral, intramuscular, subcutaneous, intradermal, or intra-nasal route. 
     
     
         14 . The method of  claim 10 , wherein the patient is suffering from a neurological disorder associated with dysfunction of one or more subtypes of nicotinic acetylcholine receptor. 
     
     
         15 . The method of  claim 14 , wherein the neurological condition is a tic disorder. 
     
     
         16 . The method of  claim 14 , wherein the neurological condition is Tourette's syndrome, presenile dementia (early onset Alzheimer's disease), senile demenia (dementia of the Alzheimer's type), Parkinson's disease, Huntington's chorea, tardive dyskinesia, hyperkinesea, mania, attention deficit disorder, attention deficit hyperactivity disorder, sleep-wake disorder, chronic-fatigue syndrome, tremor, epilepsy, neuropathic pain, nicotine addiction, anxiety, dyslexia, schizophrenia, or obsessive-compulsive disorder. 
     
     
         17 . The method of  claim 14 , wherein said administering reduces the severity of one or more symptoms associated with the neurological disorder. 
     
     
         18 . The method of  claim 14 , wherein the neurological condition is nicotine addiction, and wherein said method further comprises co-administering nicotine with the 2,2,6,6-tetramethylpiperidin-4-yl heptanoate or pharmaceutically acceptable salt thereof. 
     
     
         19 . The method of  claim 18 , wherein the nicotine is administered transdermally to the patient by a nicotine patch. 
     
     
         20 . The method of  claim 10 , wherein the 2,2,6,6-tetramethylpiperidin-4-yl heptanoate or pharmaceutically acceptable salt thereof is administered to the patient in an amount sufficient to penetrate the blood-brain barrier.