Antidyskinetic action of 3-PPP, a selective dopaminergic autoreceptor agonist, in Cebus monkeys with persistent neuroleptic-induced dyskinesias

Summary

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 (l choreic, l 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.