Comparative disposition and metabolism of paraherquamide in sheep, gerbils, and dogs.

The disposition and metabolism of paraherquamide (PHQ), a potent and broad-spectrum anthelminthic, were examined in sheep, dogs, and gerbils. The metabolism of PHQ in these species was extensive and marked by significant species differences both in vitro and in vivo. In sheep and gerbils, PHQ metabolism occurs mainly at the pyrrolidine moiety, generating several metabolites that, for the most part, retained nematodicidal activity in vitro.

A novel 4-oxo-2(E)-nonenal-derived endogenous thiadiazabicyclo glutathione adduct formed during cellular oxidative stress.

Cellular oxidative stress causes increased lipid peroxidation with the concomitant formation of DNA and protein reactive bifunctional electrophiles. Glutathione (GSH) detoxifies these bifunctional electrophiles by forming GSH adducts. Several years ago we discovered 4-oxo-2(E)-nonenal (ONE) as a major bifunctional electrophile derived from lipid hydroperoxides.

Application of LC-NMR for the study of the volatile metabolite of MK-0869, a substance P receptor antagonist.

LC-NMR was applied to identify the polar volatile metabolite of MK-0869. MK-0869, a morpholine-based compound containing a triazolone ring, is a very potent NK(1) receptor antagonist. Currently, it is in development as an anti-emesis agent in chemotherapy treatments.

Identification of metabolites of a substance P (neurokinin 1 receptor) antagonist in rat hepatocytes and rat plasma.

[3R,5R,6S]-3-(2-cyclopropyloxy-5-trifluoromethoxyphenyl)-6-phenyl-1-oxa-7-azaspiro[4.5]decane is a substance P (Neurokinin 1 receptor) antagonist. Substance P antagonists are proven in concept to have excellent potential for the treatment of major depression, and they allow superior and sustained protection from acute and delayed chemotherapy-induced emesis.