[Atypical pharmacologic characteristics of an antipsychotic drug: clozapine]

Abstract

The discovery of clozapine in the mid-sixties and the demonstration of its clinical efficacy vis-à-vis recalcitrant schizophrenia contributed to the development of specific psychopharmacological research addressing the concept of atypical antipsychotics. The research has a dual aim. First, identifying the action sites, in the brain, specific to clozapine and to conventional neuroleptics, in order to classify those drugs on the basis of the observed differences in pharmacoclinical profile (low incidence of neurological side effects, activity on schizophrenic deficiency symptoms, activity vis-à-vis certain forms of recalcitrant schizophrenia). Recent studies have used tools derived from molecular biology to determine the action sites. The results of those studies suggest that there are at least four classes of antipsychotics (reverse neuroleptics, conventional neuroleptics, atypical neuroleptics and atypical antipsychotics). The second aim of the research is to determine the behavioral effects of each of the recognized classes of medication in order to determine the neurobiological substrates specific to the elementary cognitive operations impaired in schizophrenia. There is preclinical evidence to suggest that, in each area investigated (low incidence of neurological side effects, negative symptoms, cognitive symptoms), clozapine, a "dirty" drug, acts on different neurotransmission systems. The research thus aims to determine the pharmacological profile of the drugs of the future, designed to treat the cognitive deficiencies specific to the various types of schizophrenia.