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.