The selective dopamine antagonist properties of BRL 34778: a novel substituted benzamide

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Abstract
BRL 34778, exo-4-amino-5-chloro-2-methoxy-N-[9-(4-fluorophenylmethyl)-9-azabicyclo(3.3.1)non-3-yl]-benz amide, is a very potent and specific dopamine D2-receptor antagonist. It exhibits a Ki value of 2.14 nM for dopamine D2-receptors but much lower affinity for D1-(Ki 5700 nM) and for many other receptor types. Its action is potent and of long duration in models for antipsychotic activity (4 h ED50s PO are 0.017 mg/kg for antagonism of apomorphine-induced climbing in mice and 0.028 mg/kg for antagonism of amphetamine-induced locomotion in rats). In contrast to its high potency in models for antipsychotic activity, BRL 34778 is much weaker in models for extrapyramidal effects and sedation (4 h ED50s PO are 2.4 mg/kg for inducing catalepsy in rats and 1.14 mg/kg for inhibition of rearing behaviour in rats). These data indicate potent activity of BRL 34778 in models for antipsychotic activity but low activity in models for extrapyramidal effects and sedation.