Atypical antipsychotic drugs: The 5-HT2/DA2 ratio

There has been considerable interest in clozapine, an atypical antipsychotic drug which has not been reported to produce tardive dyskinesia, produces fewer extrapyramidal symptoms, and is a more effective antipsychotic drug in decreasing positive and negative symptoms than any of the typical neuroleptic drugs. Clozapine has been reported to have superior efficacy in treatment-resistant schizophrenia as well as typical schizophrenia. Along with those benefits, it also does not produce serum prolactin elevations in man. A common mechanism may explain the many clinical differences between clozapine and typical antipsychotic drugs. It has been proposed that clozapine produces depolarization inactivation of the dopamine (DA) neurones in the striatum but not the nucleus accumbens. The ability of clozapine to block DA₂ receptors in vitro is in accord with its clinical potency which suggests that DA₂ receptor blockade is not involved in its clinical advantages. It appears that 5-HT may be of major importance to the action of atypical antipsychotic drugs via a variety of mechanisms. This further supports a role of 5-HT in schizophrenia and other psychotic illnesses.