Differences in the incidence of adverse drug reactions to trimethoprim-sulfamethoxazole and dapsone may result from differences in the formation, disposition, toxicity, and/or detoxification of their hydroxylamine metabolites. In this study, we examine whether differences in the biochemical processing of sulfamethoxazole hydroxylamine (SMX-NOH) and dapsone hydroxylamine (DDS-NOH) by erythrocyte...

Previous studies have shown that 6-methoxy-8-hydroxylaminoquinoline (MAQ-NOH), an N-hydroxy metabolite of the antimalarial drug, primaquine, is a direct-acting hemolytic agent in rats. To investigate the mechanism underlying this hemolytic activity, the effects of hemotoxic concentrations of MAQ-NOH on rat erythrocyte sulfhydryl status, membrane lipids, skeletal proteins, and morphology have be...

The newer antipsychotics olanzapine and clozapine share a number of structural and functional similarities. However, unlike clozapine, which induces agranulocytosis in about 1% of treated patients, olanzapine is not normally known to cause hematological adverse effects. The hematological effects of olanzapine have been scrutinized in several trials, none of which have found any evidence of hemo...

Although antagonism of mesolimbic dopamine D2 receptors by neuroleptics such as haloperidol attenuates positive symptoms of schizophrenia, a significant population of “resistant” patients fails to respond while negative and cognitive symptoms are little modified. Furthermore, concomitant blockade of striatal D2 receptors is associated with extrapyramidal motor side effects. The superior “atypic...