ABSTRACT
It has been clear since the discovery of the antidopaminergic properties of chlorpromazine by Carlsson in the early 1960s that this pharmacological activity, and more specifically blockade of dopamine D2 receptors, is shared by all known antipsychotic drugs. Indeed there is a clear correlation between clinically active plasma concentrations of these drugs and their affinity for the D2 receptor. More recently, antipsychotics have been developed that combine D2 receptor antagonist activity with other pharmacological activities, notably 5-HT2 receptor antagonism, with the aim of generating a broader spectrum of antipsychotic activity or a better side effect profile compared with conventional antipsychotic drugs. This strategy was inspired by clinical experience with clozapine, an atypical antipsychotic agent with a rather broad specificity toward a number of monoamine receptors, and led to the introduction of risperidone, olanzapine, quetiapine and others. On the other hand, other drugs that share the atypical clinical profile of clozapine, such as amisulpride and remoxipride, are very specific D2 receptor antagonists.
