New antipsychotics - A review of their current status and clinical potential

This review summarises the preclinical and clinical pharmacology of antipsychotics that are on the verge of introduction into clinical practice by juxtaposition of these data with the information that is already available for clozapine and risperidone. The pharmacology of clozapine is characterised by low affinity for and occupancy of dopamine D-2 receptors. Furthermore, the locus of action of clozapine may lie at a number of other sites, possibly D-4 or serotonin 5-HT2 receptors. Risperidone is characterised by a high D-2 receptor affinity and occupancy and a particularly high 5-HT2 receptor occupancy. Some investigators postulate that the action of these drugs at 5-HT2 receptors is responsible for their efficacy against the negative symptoms of schizophrenia and the low incidence of extrapyramidal adverse effects associated with their use. The effects of olanzapine on receptor systems lie between those of classical antipsychotics and clozapine. The behavioural profile of the drug is atypical, and clinical response is associated with low D-2 receptor occupancy. Quetiapine (ICI-204636; Seroquel(TM)) is also behaviourally an atypical antipsychotic. Its receptor binding profile is one of broad spectrum and low affinity, but rank potencies are the same as those of clozapine. Sertindole and ziprasidone seem to be high affinity D-2 and 5-HT2 receptor antagonists, and share many of the properties of risperidone. Much of the clinical information on olanzapine, quetiapine, sertindole and ziprasidone is not in the public domain, but early indications are that all these drugs are useful and well tolerated, while the clinical information may not discriminate one from another, their introduction will make the need to resort to classical antipsychotics less justifiable in a wider range of clinical circumstances.