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ICI 204, 636: A New Atypical Antipsychotic Drug

Published online by Cambridge University Press:  06 August 2018

Steven R. Hirsch*
Affiliation:
Charing Cross and Westminster Medical School, London
Christopher G. G. Link
Affiliation:
Zeneca Pharmaceuticals, Mereside
Jeffrey M. Goldstein
Affiliation:
CNS Clinical Research, Zeneca Pharmaceuticals, Wilmington, Delaware, USA
Lisa A. Arvanitis
Affiliation:
CNS Clinical Research, Zeneca Pharmaceuticals, Wilmington, Delaware, USA
*
Professor Steven R. Hirsch, Department of Psychiatry, Charing Cross and Westminster Medical School, London W6 8RP

Extract

The therapeutic effects of ‘classic’ (typical) antipsychotic agents lie in their ability to block central dopaminergic receptors – a property that is also responsible for the frequent occurrence of undesirable extrapyramidal side-effects (EPS). In contrast to these typical agents, clozapine alone has distinguished itself in humans – by virtue of its enhanced antipsychotic action and lack of concurrent EPS – as an atypical antipsychotic. However, the use of clozapine has been limited by the occurrence of agranulocytosis and, to a lesser extent, seizures (Alvir et al, 1993; Haring et al, 1994). The mechanism underpinning the atypical profile of clozapine remains elusive. One hypothesis suggests that it lies in clozapine's higher serotonin 5-HT2: D2 binding ratio, when compared with typical agents – a factor being considered as a predictor of atypicality (Meltzer, this issue; Meltzer et al, 1989). However, an emerging view is that it is not a single pharmacological action, but rather multiple properties that may define an atypical, clozapine-like compound (Lieberman, 1993).

Type
Research Article
Copyright
Copyright © 1996 The Royal College of Psychiatrists 

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