Antidyskinetic action of 3-PPP, a selective dopaminergic autoreceptor agonist, in Cebus monkeys with persistent neuroleptic-induced dyskinesias.
Four Cebus apella monkeys with persistent dyskinetic movements induced by earlier long-term administration of haloperidol were subjected to a trial of the dyskinesia-modifying effects of a novel dopamine autoreceptor agonist 3-PPP (3[3-hydroxyphenyl]-N-n-propyl-piperidine). Three monkeys had choreic dyskinesia involving trunk and extremities whereas one had a buccolingual form including tongue protrusion with choreoathetotic twitching and twisting movements of the tongue. Two monkeys (1 choreic, 1 buccolingual) responded with dose-dependent symptom alleviation to 3-PPP, 1-4 mg/kg, with no signs of concomitant sedation or catalepsy. In the monkey with buccolingual dyskinesia all dyskinetic signs disappeared completely 2 hours after 2 mg/kg of 3-PPP. This animal participated in a separate study where the same doses of 3-PPP but also its enantiomers were given. The (-) enantiomer was a more potent antidyskinetic agent than the (+) enantiomer, the racemate falling between these two. Four mg/kg of the (+) enantiomer precipitated an amphetamine-like excitation and after 4 hours aggravation of dyskinesia was noted. These observations support the notion that the (+) enantiomer has both postsynaptic and presynaptic stimulatory effects, whereas the (-) enantiomer acts as a presynaptic dopamine receptor agonist.
D000818:Animals; D002428:Cebus; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D005260:Female; D005476:Fluphenazine / Q000633:toxicity*; D006220:Haloperidol / Q000633:toxicity*; D008297:Male; D010880:Piperidines / Q000627:therapeutic use*; D013237:Stereoisomerism
D010880:Piperidines; C026539:preclamol; D006220:Haloperidol; D005476:Fluphenazine