Positron Emission Tomography of in-vivo Binding Characteristics of Atypical Antipsychotic Drugs

Abstract

Several types of neuroreceptors are of interest with respect to antipsychotic activity, in particular the D2, D1, and 5-HT2 receptors. Among currently prescribed antipsychotic drugs, some have an affinity for a broad range of neuroreceptors, while others are more selective for the D2 receptor (Hytell et al, 1985). The most widely accepted hypothesis of neuroleptic drug action is that antipsychotic effects are mediated by a blockade of the dopamine receptors (Carlsson & Lindqvist, 1963; van Rossum, 1966; Creese et al, 1976; Seeman et al, 1976; Peroutka & Snyder, 1980). This hypothesis has been supported by consistent findings of high D2 receptor occupancy in positron emission tomography (PET) studies of patients treated with antipsychotic drugs (Farde et al, 1986; Smith et al, 1988; Baron et al, 1989). At the same time, the risk of extrapyramidal side-effects (EPS) seems particularly high in patients with occupancy above 80% (Farde et al, 1992) (Fig. 1).