Metabolism of methamphetamine, amphetamine and p-hydroxymethamphetamine by rat-liver microsomal preparations in vitro.
Methamphetamine N-demethylation and p-hydroxylation activities of rat liver were located mainly in the microsomal fraction. The Km values for methamphetamine and p-hydroxymethamphetamine demethylations were 1.0 and 1.6 mM, respectively. The Km value for amphetamine p-hydroxylation was 10.2 microM; substrate inhibition occurred at high substrate concn. Two Km values were obtained for the aromatic hydroxylation of methamphetamine (10.6 microM and 2.2 mM). N-Demethylation of methamphetamine and p-hydroxymethamphetamine were depressed in rats pretreated with 3-methylcholanthrene, CoCl2 or SKF 525-A. In rats pretreated with phenobarbital, methamphetamine demethylase was induced and p-hydroxymethamphetamine demethylase was depressed. The p-hydroxylation of methamphetamine and amphetamine in rats pretreated with phenobarbital, CoCl2, SKF 525-A or iprindole were depressed.
D000661:Amphetamine / Q000378:metabolism*; D000818:Animals; D008401:Gas Chromatography-Mass Spectrometry; D066298:In Vitro Techniques; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000378:metabolism*; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity
D008694:Methamphetamine; C005877:pholedrine; D000661:Amphetamine; D006899:Mixed Function Oxygenases; D010089:Oxidoreductases, N-Demethylating