DOPAMINE-D1 (SCH-23390) AND DOPAMINE-D2 (HALOPERIDOL) ANTAGONISTS IN DRUG-NAIVE MONKEYS

The ability of dopamine D1 antagonists to produce acute extrapyramidal syndromes (EPS) in nonhuman primates is unclear. Some studies in monkeys show that D1 antagonists produce acute dystonia, whereas other studies do not report these effects. The central issues that have yielded conflicting results revolve around prior treatment status (neuroleptic-naive versus neuroleptic sensitized) and route of administration (oral versus parenteral). In this study, separate groups of neuroleptic drug-naive cebus monkeys were tested once weekly with intramuscularly administered SCH 23390, a D1 antagonist, or haloperidol, a D2 antagonist, across a dose range of 0.01-0.25 mg/kg, and a saline control. Both active drugs, but not saline, produced clinically identical syndromes of acute dystonia and bradykinesia, though haloperidol induced higher symptom scores over a longer duration. Sedation and locomotor activity were unchanged by SCH 23390, but decreased with haloperidol. Factors regarding acute EPS liability in nonhuman primate models and clinical implications in man are discussed.