DELTA OPIOID AGONIST, MU OPIOID ANTAGONIST COMPOSITIONS AND METHODS FOR TREATING PARKINSONS DISEASE
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.
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.