Understanding the mechanism of action of atypical antipsychotic drugs. A review of compounds in use and development.

The thrust of development of new antipsychotic drugs has been to identify new compounds that have enhanced antipsychotic efficacy and have lesser side-effects than standard neuroleptic compounds. Drug development strategies no longer concentrate on D2 receptor antagonism but aim to produce novel compounds. The following have been pursued: (a) selective dopamine receptor antagonists; (b) serotonin receptor agonists and antagonists (5-HT1a,e'5-HT2,5-HT3) or mixed 5-HT2-D2 receptor antagonist; (c) selective dopamine agonists or partial agonists; and (d) sigma-site and excitatory amino-acid antagonists. Such compounds are at various stages of development. The only drug which has truly distinguished itself as 'atypical' is clozapine. Its mechanism of action is unknown and the search for it, in large part, has been the impetus for development of the compounds listed above.