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.

[1]  G. Jones,et al.  Identification of a nitrone as an in vitro metabolite of N-methylamphetamine. , 1978, Biomedical mass spectrometry.

[2]  A. Cho,et al.  Pathways of metabolism of amphetamine and related compounds. , 1978, Life sciences.

[3]  P. Murphy,et al.  Aromatic hydroxylation of amphetamine with rat liver microsomes, perfused liver, and isolated hepatocytes. , 1978, Biochemical pharmacology.

[4]  R. T. Coutts,et al.  Metabolism in vitro of N-methylamphetamine with rat liver homogenates. , 1977, Biochemical pharmacology.

[5]  R. Prough,et al.  The relative participation of liver microsomal amine oxidase and cytochrome P-450 in N-demethylation reactions. , 1977, Archives of biochemistry and biophysics.

[6]  R. T. Coutts,et al.  Metabolic N-Oxidation of Primary and Secondary Aliphatic Medicinal Amines , 1977 .

[7]  P. Albro.  Determination of protein in preparations of microsomes. , 1975, Analytical biochemistry.

[8]  J. Jonsson.  Hydroxylation of amphetamine to parahydroxyamphetamine by rat liver microsomes. , 1974, Biochemical pharmacology.

[9]  H. Rommelspacher,et al.  The hydroxylation of D-amphetamine by liver microsomes of the male rat. , 1974, Biochemical pharmacology.

[10]  A. Beckett,et al.  Synthesis of N-alkyl-N-hydroxyamphetamines and related nitrones , 1973 .

[11]  F. Kadlubar,et al.  Reduced pyridine nucleotide-dependent N-hydroxy amine oxidase and reductase activities of hepatic microsomes. , 1973, Archives of biochemistry and biophysics.

[12]  A. Y. Lu,et al.  Pregnenolone-16α-carbonitrile: A new type of inducer of drug-metabolizing enzymes , 1972 .

[13]  J. Caldwell,et al.  Metabolism of [14C]methamphetamine in man, the guinea pig and the rat , 1972 .

[14]  A. Beckett.  Metabolic Oxidation of Aliphatic Basic Nitrogen Atoms and their α-Carbon Atoms , 1971 .

[15]  A. Beckett,et al.  Urinary excretion kinetics of methylamphetamine in man , 1965 .

[16]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.