[Use of pharmacological data in the choice of antipsychotic drugs]

The choice of antipsychotic drug should be based on experimental data from biochemistry and animal pharmacology, according to the targeted clinical effects. However, owing to the lack of good animal models of mental disease only the clinical approach can validate the antipsychotic efficacy of a drug. Within the theoretical frame of dopaminergic activity in schizophrenia a specificity of the various neuroleptics according to the four dopaminergic structure is evidenced through cellular electrophysiological studies. Classical provisional pharmacology of antipsychotics uses in animals on the one hand naturalistic observation tests, and on the other hand interactions vis-à-vis behaviours induced by stimulating dopaminergic agents, as amphetamine and apomorphine. Differential analysis of antipsychotic effects on each of those behaviours allows to discriminate between the various neuroleptics and to refine their pharmacological profile, specially to predict a disinhibitory action with some of them. Progress in the identification, localisation, number modification of target receptors of different neurotransmitters as well as the biochemical response to their stimulation by agonist or antagonist allows to delineate more precisely the neurobiochemical action of antipsychotic drugs. On top of antidopaminergic D2 effect, anti D1 effect begin to be investigated. More over the role of antiserotonergic 5-HT2 and central anticholinergic actions seems to be important in the "atypical" aspect of some neuroleptic drugs. More recently, contributions from molecular biology made it possible to clone and to synthetize five subtypes of dopaminergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)