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Antipsychotic efficacy: Relationship to optimal D2-receptor occupancy

Published online by Cambridge University Press:  16 April 2020

Luca Pani ,
Luigi Pira  and
Giorgio Marchese
Luca Pani*
Affiliation:
PharmaNess S.c.a.r.l, Technological Park - Sardegna Ricerche, Pula (CA), Italy C.N.R., Institute of Biomedical Technology Sect. Cagliari, c/o Technological Park - Sardegna Ricerche, Pula (CA), Italy
Luigi Pira
Affiliation:
PharmaNess S.c.a.r.l, Technological Park - Sardegna Ricerche, Pula (CA), Italy
Giorgio Marchese
Affiliation:
PharmaNess S.c.a.r.l, Technological Park - Sardegna Ricerche, Pula (CA), Italy
*
*Corresponding author. PharmaNess S.c.a.r.l, and C.N.R., Institute of Biomedical Technology, Sect. Cagliari c/o PharmaNess S.c.a r.l., Building 5, Technological Park - Sardegna Ricerche, 09010 Pula (Cagliari), Italy. Tel.: +39 070 924 2029; fax: +39 070 924 2206. E-mail addresses: [email protected] (L. Pani), [email protected] (G. Marchese).
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Abstract

Clinically important differences exist between antipsychotic agents and formulations in terms of safety and tolerability. Features of the biochemical interaction between the antipsychotic and the D2-receptor may underlie these differences. This article reviews current information on the relationship between antipsychotic receptor occupancy and clinical response. A literature search was performed using the keywords ‘antipsychotic or neuroleptic’, ‘receptor’ and ‘occupancy’ and ‘dopamine’ and ‘D2’ supplemented by the authors’ knowledge of the literature. Imaging and clinical data have generally supported the hypotheses that optimal D2-receptor occupancy in the striatum lies in a ‘therapeutic window’ between ∼65 and ∼80%, however, pharmacokinetic and pharmacodynamic properties of a drug should also be taken into account to fully evaluate its therapeutic effects. Additional research, perhaps in preclinical models, is needed to establish D2-receptor occupancy in various regions of the brain and the optimal duration of D2-receptor blockade in order to maximise efficacy and tolerability profiles of atypical antipsychotics and thereby improve treatment outcomes for patients with schizophrenia.

Keywords

AntipsychoticAtypicalDopamineReceptorOccupancyExtrapyramidal symptoms
Type
Review
Information
European Psychiatry , Volume 22 , Issue 5 , July 2007 , pp. 267 - 275
Copyright
Copyright © Elsevier Masson SAS 2007

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