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

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.
AuthorsJ E Häggström, L M Gunne, A Carlsson, H Wikström
JournalJournal of neural transmission (J Neural Transm) Vol. 58 Issue 3-4 Pg. 135-42 ( 1983) Austria
PMID6663299 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Piperidines
  • preclamol
  • Haloperidol
  • Fluphenazine
Topics
  • Animals
  • Cebus
  • Dose-Response Relationship, Drug
  • Dyskinesia, Drug-Induced (drug therapy)
  • Female
  • Fluphenazine (toxicity)
  • Haloperidol (toxicity)
  • Male
  • Piperidines (therapeutic use)
  • Stereoisomerism

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