Motor effects of the partial dopamine agonist (-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine (preclamol) in Parkinson's disease.
The motor effects of the partial dopamine agonist (-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine [(-)-3-PPP, preclamol] were evaluated in nine patients with Parkinson's disease using a double-blind, placebo-controlled design. (-)-3-PPP monotherapy had an antiparkinsonian effect in five of nine patients at a mean dose of 37 +/- 10 mg intramuscularly. The co-administration of (-)-3-PPP and a mildly dyskinetic dose of levodopa, infused intravenously at steady-state, resulted in complete suppression of dyskinesias and reemergence of parkinsonian signs in two of seven patients. These dopamine antagonist effects of (-)-3-PPP occurred at relatively low (2.5 and 5 mg) doses. Our results suggest that partial dopamine agonists can exert agonist or antagonist activity in parkinsonian patients depending on concurrent dopaminergic tone. Although this dual action of (-)-3-PPP and other partial agonists could be therapeutically important on theoretical grounds, the small number of patients manifesting a clinically significant response and the frequently inconsistent effects could indicate that this class of agents may have relatively limited clinical utility.
Metman
L V
LV
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Sethy
V H
VH
Roberts
J R
JR
Bravi
D
D
Hoff
J I
JI
Mouradian
M M
MM
Chase
T N
TN
D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007273:Injections, Intramuscular; D007980:Levodopa / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*
D000978:Antiparkinson Agents; D010880:Piperidines; D007980:Levodopa; C026539:preclamol