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5-HT2A receptor blockade in patients with schizophrenia treated with risperidone or clozapine

A SPET study using the novel 5-HT2A ligand 1231-5-1-R-91150

Published online by Cambridge University Press:  03 January 2018

Michael J. Travis ,
Geraldo F. Busatto ,
Lyn S. Pilowsky ,
Rachel Mulligan ,
Paul D. Acton ,
Sveto Gacinovic ,
John Mertens ,
Dirk Terrière ,
Durval C. Costa  and
Peter J. Ell
...Show all authors
Michael J. Travis
Affiliation:
Institute of Psychiatry, London
Geraldo F. Busatto
Affiliation:
Institute of Psychiatry, London
Lyn S. Pilowsky
Affiliation:
Institute of Psychiatry, London
Rachel Mulligan
Affiliation:
Institute of Nuclear Medicine, London
Paul D. Acton
Affiliation:
Institute of Nuclear Medicine, London
Sveto Gacinovic
Affiliation:
Institute of Nuclear Medicine, London
John Mertens
Affiliation:
Biochem, Eng, VVB Cyclotron, Brussels, Belgium
Dirk Terrière
Affiliation:
Biochem, Eng, VVB Cyclotron, Brussels, Belgium
Durval C. Costa
Affiliation:
Institute of Nuclear Medicine, London
Peter J. Ell
Affiliation:
Institute of Nuclear Medicine, London
Robert W. Kerwin
Affiliation:
Institute of Psychiatry, London
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Abstract

Background

5-HT2A receptor antagonism may be crucial to the action of atypical antipsychotics. Previous work has related 5-HT2A receptor blockade to clinical efficacy and protection from extrapyramidal side-effects.

Method

We developed a SPET imaging protocol for assessing 5-HT2A receptor binding using the selective ligand 1231-5-1-R91150. Six healthy volunteers, five clozapine- and five risperidone-treated subjects with DSM–IV schizophrenia were studied. Multi-slice SPET was performed on each subject.

Results

Cortex: cerebellum ratios were significantly lower in both clozapine-and risperidone-treated subjects compared with the healthy volunteers in all cortical regions. There was no difference in occupancy between the two drug-treated groups. No correlation was found between the percentage change in the Global Assessment Scale (GAS) and 5-HT2A receptor binding indices in the drug-treated groups.

Conclusions

Clozapine and risperidone potently block 5-HT2A receptors in vivo. The lack of relationship between receptor binding indices and change in GAS suggests that 5-HT2A receptor blockade may be unrelated to clinical improvement. Future studies will substantiate this finding by studying 5-HT2A receptor binding in large groups of patients treated with both typical and novel atypical antipsychotics.

Type
Papers
Information
The British Journal of Psychiatry , Volume 173 , Issue 3 , September 1998 , pp. 236 - 241
Copyright
Copyright © 1998 The Royal College of Psychiatrists 

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