Anti-dopaminergic and anti-muscarinic effects of dibenzodiazepines: relationship to drug induced Parkinsonism

Abstract

1. The anti-dopaminergic effects of several dibenzodiazepines were examined on the dopamine-stimulated adenylate cyclase in rat striatal homogenates. The "cis" isomer of clozapine, HF-2046, was the most potent in this respect and perlapine, which is devoid of neuroleptic activity, was the weakest. 2. The anti-muscarinic effects of the same compounds were measured by using the muscarinic affinity label 3H-propylbenzilylcholine mustard. HF-2046 was the most potent and loxapine the least potent of the drugs used. 3. The anti-dopaminergic effects of the drugs correlate well with neuroleptic but not with extrapyramidal effects. The anti-dopaminergic/anti-muscarinic ratio, however, correlates well with extrapyramidal rather than neuroleptic effects.