生物活性：Clozapine N-oxide is a major metabolite of Clozapine noted to decrease SR-2A (5-HT2 serotonin receptor) density in vitro.
Clozapine N-oxide was noted to decrease 5-HT2 serotonin receptor density in rat primary cortical cells and human hippocampal SHS5Y5 neuroblastoma cells.
in vitro: Clozapine and N-desmethylclozapine antagonized 5-HT-stimulated phosphoinositide hydrolysis with IC50 values of 110 and 29.4 nM, respectively. Clozapine N-oxide was less potent .
in vivo: When administered clozapine, mean CNO plasma concentrations of 17.7 +/- 16.4 ng/ml were slightly lower than the other clozapine metabolite-desmethylclozapine (DCLOZ) plasma levels of 24.4 +/- 8.6 ng/ml at the 12 hour time point. When CNO was administered, plasma concentrations at the 12 hour time point of clozapine were twice the amount of CNO (28.1 +/- 8.9 ng/ml vs 14.4 +/- 8.8 ng/ml) . Clozapine and its metabolite clozapine-N-oxide (0.5 mg/kg) were administered intraperitoneally to guinea-pigs. Significant amounts of clozapine were detected in plasma, liver, frontal cortex and caudate after clozapine-N-oxide administration .