Delta opioid agonist, mu opioid antagonist compositions and methods for treating parkinsons disease

Abstract

The present invention provides for compositions and methods for the treatment of Parkinson's disease comprising a compound of formula (i): or a pharmaceutically effective salt or ester thereof alone or in combination with L-DOPA to provide a synergistic effect, thereby providing methods of (1) treating patients with Parkinson's Disease for whom L-DOPA is no longer effective, (2) treating patients with Parkinson's Disease who developed dyskinesia due to L-DOPA, (3) treating patients with Parkinson's Disease who have are receiving deep brain stimulation and (4) treating patients with Parkinson's Disease whose symptoms interfere with activities of daily living.

That which is claimed is: 
     
         1 . A method of treatment for a subject with Parkinson's disease experiencing prolonged L-DOPA treatment and increasing episodes of “off-time,” the method comprises supplementing administered reduced amount of L-DOPA dose with therapeutically effective amount of formula 
       
         
           
           
               
               
           
         
         4-((alpha-R)-alpha-(2S,5R)-2,5-Dimethyl-4-(3-fluorobenzyl)-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide or a pharmaceutically acceptable salt or ester thereof to maintain or achieve an antiparkinsonian effect. 
       
     
     
         2 . The method of  claim 1  wherein the compound of formula (i) is administered in a dose ranging from about 1 to about 100 mg/kg per day. 
     
     
         3 . The method of  claim 1 , wherein the reduced amount of L-DOPA ranges from an amount from 1 to 10 mg/kg/day of L-DOPA. 
     
     
         4 . The method of  claim 2  wherein the compound of formula (i) is administered in a dose ranging from about 5-20 mg/kg per day. 
     
     
         5 . The method of  claim 4  wherein the administered formula (i) results in prolongation of the duration of effect of a single sub-therapeutic dose of L-DOPA. 
     
     
         6 . A method of treatment for a subject with Parkinson's disease subjected to deep brain stimulation, the method comprising postsurgical administration of formula (i): 
       
         
           
           
               
               
           
         
         4-((alpha-R)-alpha-((2 S, 5R)-2,5-Dimethyl-4-(3-fluorobenzyl)-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide or a pharmaceutically acceptable salt or ester. 
       
     
     
         7 . The method of  claim 6 , wherein the compound of formula (i) is administered in a dose ranging from about 1 to about 100 mg/kg/day. 
     
     
         8 . The method of  claim 7 , further comprising a dose of L-DOPA in an amount from about 1 to 10 mg/kg/day.