REVIEW OF THE NEUROLEPTIC CHEMOTHERAPY DURING 40 YEARS

Since the Delay, Deniker and Harl's initial report, the story of neuro leptics comprises three distinct periods. Firstly the discovery of sev eral drugs and of their clinical effects occured and was followed only a posteriori by definition. In 1963, Carlsson supported a hyperdopami nergic theory of psychoses. A second period began with many biochemica l hypotheses concerning schizophrenia (serotoninergic, noradrenergic, glutamatergic hypothesis...). These hypothesis should be considered as << not proven >> but their presence means that schizophrenia is most probably a multineuro-transmetter-system disease and that several crit ical issues remain to be clarified concerning the dopamine hypothesis of schizophrenia. During these years (1960-1980) almost all << availab le compounds >> have been marketed. In the eighties a third period see ms to begin. The notions of refractory schizophrenia and of a typical neuroleptics have been described. An << atypical >> neuroleptic is an effective antipsychotic drug without inducing concomitant extrapyramid al side effects. The concept of atypicity has becomed a new vista for research of new antipsychotic drugs. The notions of partial dopaminerg ic agonism, antagonism of D4 receptor, selective 5HT2 antagonism must be viewed as a source of future research and therapeutic improvement.