Suppression of neuroleptic-induced persistent abnormal movements in Cebus apella monkeys by enantiomers of 3-PPP.
Effects of the enantiomers of the dopamine (DA) autoreceptor agonist 3-PPP (0.5-8.0 mg/kg body weight, i.m.) were studied in three Cebus apella monkeys with persistent abnormal movements induced by prior long-term treatment with fluphenazine enanthate. In 2 of the animals, (-)-3-PPP abolished the abnormal movements while producing only negligible acute motor effects (trembling and stereotypy). (+)-3-PPP, administered to one of these monkeys, also produced a dose-dependent suppression of the persistent abnormal movements, along with the appearance of acute motor signs including tongue protrusions, hyperkinesia, and stereotypy; at the highest dose, there was a biphasic effect. In the first phase, there were pronounced acute motor signs but no persistent abnormal movements. In the second phase, there were neither acute nor persistent abnormal movements. One monkey was unaffected by (-)-3-PPP or low doses of (+)-3-PPP; a higher dose (4 mg/kg) produced hyperkinesia and increased persistent abnormal movements in one experimental setting. The suppression of neuroleptic-induced persistent abnormal movements by 3-PPP enantiomers may be related to their ability to act as autoreceptor agonists, while the acute motor signs produced by higher doses of (+)-3-PPP may be due to activation of postsynaptic DA receptors. The present findings suggest that (-)-3-PPP and drugs with a similar pharmacological profile might be effective as symptomatic treatments for tardive dyskinesia, with little chance of inducing acute extrapyramidal side-effects.
Kovacic
B
B
Department of Neurology, Lafayette Clinic, Detroit.
Le Witt
P
P
Clark
D
D
D000818:Animals; D002428:Cebus; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D005260:Female; D005476:Fluphenazine; D010880:Piperidines / Q000008:administration & dosage*; D013237:Stereoisomerism; D013997:Time Factors
D010880:Piperidines; C026539:preclamol; D005476:Fluphenazine