The prospects of new antipsychotic principles

Biological schizophrenia research has been dominated by the dopamine hypothesis for decades, but in recent years a more diversified view has gained increasing attention. Several neurotransmitters are now being discussed, and especially their interaction in complex circuitries. The demonstration of an atypical profile of clozapine (Leponex®), with lessened extrapyramidal side effects and somewhat increased efficacy, has stimulated this research field considerably. This agent has high affinity not only for the different dopamine receptor subtypes, but also for serotonergic, alpha-adrenergic and muscarinic receptors. Different workers have stressed one or more of these sites as being of major importance for the atypical profile of clozapine, and several drug companies have made attempts to mimic the profile of clozapine by developing molecules with affinity for these receptors in varying proportions. A number of such agents have reached or will soon reach the market and appear to be promising, even though they may not match clozapine in terms of atypicality.