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Antipsychotic drugs (APD) are widely prescribed for the treatment of schizophrenia. The APD are differentiated into typical and atypical based on the lower incidence of extra-pyramidal side-effects associated with the newer atypical APD. It was suggested that atypicality may arise from an interaction with the 5-hydroxytryptamine (5-HT)(2) receptor and specifically on the 5-HT(2):dopamine D(2) affinity ratio. It is now realised that multiple subtypes of these receptors exist and that in addition, atypical APD interact with many monoamine receptors. The aim of the present study was to characterise the interaction of APD with a variety of monoamine receptors in terms of both affinity and efficacy. The data produced has highlighted that the atypical profile of APD such as olanzapine and clozapine may reflect antagonism of the 5-HT(2A) and 5-HT(2C) receptors, whilst that of, ziprasidone and quetiapine may reflect partial agonist activity at the 5-HT(1A) receptor, and that of aripiprazole may reflect partial agonist activity at the 5-HT(1A) receptor as well as is its claimed partial agonist activity at the dopamine D(2) receptor.


Martyn D Wood, Claire Scott, Kirsten Clarke, Katherine J Cato, Nisha Patel, Jennie Heath, Angela Worby, Laurie Gordon, Lorraine Campbell, Graham Riley, Ceri H Davies, Andrew Gribble, Declan N C Jones. Pharmacological profile of antipsychotics at monoamine receptors: atypicality beyond 5-HT2A receptor blockade. CNS & neurological disorders drug targets. 2006 Aug;5(4):445-52

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PMID: 16918396

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