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Coleman MD, Kuhns MJ. Bioactivation of the cyanide antidote 4-aminopropiophenone (4-PAPP) by human and rat hepatic microsomal enzymes: effect of inhibitors. Environ Toxicol Pharmacol. 1999;7(1):75-80doi: 10.1016/s1382-6689(98)00052-0.
Coleman, M. D., & Kuhns, M. J. (1999). Bioactivation of the cyanide antidote 4-aminopropiophenone (4-PAPP) by human and rat hepatic microsomal enzymes: effect of inhibitors. Environmental toxicology and pharmacology, 7(1), 75-80. https://doi.org/10.1016/s1382-6689(98)00052-0
Coleman, M D, and Kuhns, M J. "Bioactivation of the cyanide antidote 4-aminopropiophenone (4-PAPP) by human and rat hepatic microsomal enzymes: effect of inhibitors." Environmental toxicology and pharmacology vol. 7,1 (1999): 75-80. doi: https://doi.org/10.1016/s1382-6689(98)00052-0
Coleman MD, Kuhns MJ. Bioactivation of the cyanide antidote 4-aminopropiophenone (4-PAPP) by human and rat hepatic microsomal enzymes: effect of inhibitors. Environ Toxicol Pharmacol. 1999 Mar;7(1):75-80. doi: 10.1016/s1382-6689(98)00052-0. PMID: 21781912.
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Environ Toxicol Pharmacol. 1999 Mar;7(1):75-80. doi: 10.1016/s1382-6689(98)00052-0.

Bioactivation of the cyanide antidote 4-aminopropiophenone (4-PAPP) by human and rat hepatic microsomal enzymes: effect of inhibitors.

Environmental toxicology and pharmacology

M D Coleman, M J Kuhns

Affiliations

  1. Mechanisms of Drug Toxicity Group, Pharmaceutical Sciences Institute, Aston University, Aston Triangle, Birmingham B4 7ET, UK.

PMID: 21781912 DOI: 10.1016/s1382-6689(98)00052-0

Abstract

The bioactivation of the cyanide antidote methaemoglobin former 4-aminopropiophenone (4-PAPP) was studied using rat and human microsomes. With rat liver and NADPH in single and two-compartment systems, dapsone and benzocaine were more potent methaemoglobin generators compared with 4-PAPP. In the single compartment studies, the order of potency of inhibition of 4-PAPP-mediated methaemoglobin formation was cimetidine (1.5 mM)>isoniazid (500 μM)/diethyldithiocarbamate (DDC, 1 mM)>erythromycin (500 μM). Human liver microsomal activation of 4-PAPP in the two-compartment system was partially inhibited by both DDC and cimetidine. These preliminary studies suggest that 4-PAPP may be metabolised by CYP 2C11, 2E1 and 3A in the rat and CYP 2C, 2E1 and probably 3A4 in man.

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