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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 K i value of 2.14 nM for dopamine D2-receptors but much lower affinity for D1-(K i 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.

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Author notes

  1. W. Campbell

    Present address: Systems General, Standard Life Assurance, 3 George St, EH2 2XZ, Edinburgh, UK

  2. P. Mitchell

    Present address: School of Pharmacy and Pharmacology, University of Bath, BA2 7AY, Bath, UK

  3. P. Needham

    Present address: Research Department, The Boots Company p.l.c., NG2 3AA, Nottingham, UK

Authors and Affiliations

  1. Beecham Pharmaceuticals Research Division, CM19 5AD, Harlow, Essex, UK

    F. Brown, W. Campbell, M. S. G. Clark, D. S. Graves, M. S. Hadley, J. Hatcher, P. Mitchell, P. Needham, G. Riley & J. Semple

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  1. F. Brown
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Brown, F., Campbell, W., Clark, M.S.G. et al. The selective dopamine antagonist properties of BRL 34778: a novel substituted benzamide. Psychopharmacology 94, 350–358 (1988). https://doi.org/10.1007/BF00174689

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  • DOI: https://doi.org/10.1007/BF00174689

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