Potent inhibition of MAO mediated propranolol metabolism by dimethyl sulfoxide in Hep G2 cells.
This communication reports on the effects of dimethyl sulfoxide (DMSO) on the oxidative metabolism of propranolol by the homogenate of the human hepatoma cell line Hep G2. The formation of multiple metabolites was monitored in the absence and presence of 0.1 to 2.0% of DMSO. For the primary cytochrome P450-mediated pathways, ring oxidation was significantly reduced by 1.3 to 2.0% DMSO, whereas side-chain oxidation was not affected. A gradual inhibition of the oxidative deamination of N-desisopropylpropranolol to its glycol metabolite was seen with 20% inhibition at a DMSO concentration of 0.1% and a maximum 75% inhibition at a DMSO concentration of 0.7%. This highly selective inhibitory effect of DMSO on oxidative drug metabolism appears to be directed towards MAO type A.
Steiner
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Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston 29425.
Walle
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D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011433:Propranolol / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D065607:Cytochrome P-450 Enzyme Inhibitors; D008996:Monoamine Oxidase Inhibitors; D003577:Cytochrome P-450 Enzyme System; D011433:Propranolol; D004121:Dimethyl Sulfoxide