JL-13, A POTENTIAL SUCCESSOR TO CLOZAPINE, IS LESS SENSITIVE TO OXIDATIVE PHENOMENA

The oxidation behaviour of JL 13, a promising antipsychotic, was inves tigated in comparison with clozapine and loxapine, by measuring their direct ''radical scavenging'' abilities and their efficacies in inhibi ting the lipid peroxidation. In the lipid peroxidation system, the rea ctivity of these compounds with free radicals produced by gamma-irradi ation of linoleic acid may be presented as follows: JL 13 = loxapine < clozapine, In tyro enzymatic systems (HRP/GSH and HRP/H2O2/GSH) which generate the thiyl free radicals, clozapine produces a strong enhance ment of the thiyl-radical EPR signal intensity while JL 13 and loxapin e exhibit no or minimal effect on this signal, The redox potential val ues for the three derivatives confirm the spectrophotometric and EPR r esults. Following this study, we show that JE 13, although presenting a preclinical clozapine-like profile, appears less sensitive to oxidat ion than clozapine. (C) 1997 Academic Press.