PEROXIDASE-CATALYZED OXIDATION OF DIFFERENT DIBENZAZEPINE DERIVATIVES

According to a recent hypothesis suggesting the potential role of free radical formation in the clozapine-induced agranulocytosis, we have e valuated the susceptibility to the peroxidase-mediated oxidation of di fferent dibenzazepine analogues. On the one hand, compounds with an ar ylamine group such as clozapine or isoclozapine present a high reactiv ity in the horseradish peroxidase or myeloperoxidase systems and, on t he other hand, fluperlapine, though known to induce agranulocytosis, a nd other dibenzothiazepine and dibenzoxazepine derivatives appear inse nsitive to oxidation. Consequently, among tricyclic derivatives, the w ay of diaryloxa- and diarylthiazepine compounds could be an alternativ e for the development of safer drugs such as antipsychotics.