Positron Emission Tomography of<i>in-vivo</i>Binding Characteristics of Atypical Antipsychotic Drugs

Abstract

Several types of neuroreceptors are of interest with respect to antipsychotic activity, in particular the D 2 , D 1 , and 5-HT 2 receptors. Among currently prescribed antipsychotic drugs, some have an affinity for a broad range of neuroreceptors, while others are more selective for the D 2 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 &amp; Lindqvist, 1963; van Rossum, 1966; Creese et al , 1976; Seeman et al , 1976; Peroutka &amp; Snyder, 1980). This hypothesis has been supported by consistent findings of high D 2 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).