MODULATION OF THE CLOZAPINE STRUCTURE INCREASES ITS SELECTIVITY FOR THE DOPAMINE D-4 RECEPTOR

Clozapine has a more marked affinity for the recently cloned dopamine D-4 receptor than for the dopamine D-2 receptor. In the search for a s elective ligand for the dopamine D-4 receptor, useful as a pharmacolog ical tool or as a potent atypical antipsychotic, a pyridobenzodiazepin e derivative bioisoster of clozapine, JL 18, piperazinyl)-11H-pyrido[2 ,3-b][1,4]benzodiazepine, was found to be the most dopamine D-4-select ive ligand belonging to the diarylazepine class. Indeed, JL 18 binds t o the dopamine D-4 receptor with affinity up to 25 times superior to t hat for the dopamine D-2 receptor and presents reduced affinities for other receptors.