Research PaperA proposed mechanism for chlorpromazine jaundice — defective hepatic sulphoxidation combined with rapid hydroxylation
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2016, Chemico-Biological InteractionsCitation Excerpt :Some of these metabolites may contribute to chlorpromazine hepatotoxicity [71]. It has been suggested that the hydroxylated metabolites of chlorpromazine are more active than the sulfoxide metabolites in inducing jaundice [72]. It has also been shown that the mono- and di-demethylated metabolites of chlorpromazine are three and six times, respectively, more potent than the parent drug in causing the leakage of aspartate aminotransferase from isolated rat hepatocytes, while 7- and 8-hydroxychlorpromazine are slightly less potent than chlorpromazine, and sulfoxide metabolites are inactive [73].
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2013, Toxicology and Applied PharmacologyCitation Excerpt :Of these, the 7-hydroxylation pathway, catalyzed mainly by CYP2D6 and partially by CYP1A2, is considered to be the major metabolic pathway for CPZ metabolism in humans (Yeung et al., 1993; Yoshii et al., 2000). It was shown that the ring-hydroxylated metabolites of CPZ are highly potent than the sulfoxidation product in causing jaundice in humans (Watson et al., 1988). Another study showed that the demethylated metabolites, mono- and didesmethyl-CPZ, were three and six times, respectively, more potent than CPZ in causing the release of aspartate aminotransferase from isolated rat hepatocytes (Abernathy et al., 1977).
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