Jean-Frangois Liegeois*, Jacques Bruhwyler, Frangoise Rogister and Jacques Delarge Pages 471 - 501 ( 31 )
Dibenzoazepine derivatives have represented and still represent today an interesting and exciting field of investigation in medicinal chemistry. A slight modification of the tricyclic structure leads to a profound alteration of the activity profile. Indeed, clothiapine is a neuroleptic drug with strong propensity to induce extrapyramidal side effects (EPS) while clozapine possesses an atypical neuroleptic profile and produces only minimal EPS. The action mechanisms of clozapine have not been completely elucidated. Although clozapine represents a great advance in the treatment of psychiatric disorders, the induction of dramatic toxic effects has stimulated the search for an alternative to clozapine. This challenge is currently the focus of the most active efforts in contemporary neuropharmacology. This review attempts to describe the development of atypical neuroleptic drugs through the diarylazepine series, a promising and modulable class of compounds.