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

J Neural Transm. 1983;58(3-4):135-42. doi: 10.1007/BF01252800.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cebus
  • Dose-Response Relationship, Drug
  • Dyskinesia, Drug-Induced / drug therapy*
  • Female
  • Fluphenazine / toxicity*
  • Haloperidol / toxicity*
  • Male
  • Piperidines / therapeutic use*
  • Stereoisomerism

Substances

  • Piperidines
  • preclamol
  • Haloperidol
  • Fluphenazine