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Titolo:
THE DEMETHYLENATION OF METHYLENEDIOXYMETHAMPHETAMINE (ECSTASY) BY DEBRISOQUINE HYDROXYLASE (CYP2D6)
Autore:
TUCKER GT; LENNARD MS; ELLIS SW; WOODS HF; CHO AK; LIN LY; HIRATSUKA A; SCHMITZ DA; CHU TYY;
Indirizzi:
UNIV SHEFFIELD,ROYAL HALLAMSHIRE HOSP,DEPT MED & PHARMACOL SHEFFIELD S10 2JF ENGLAND UNIV CALIF LOS ANGELES,CTR HLTH SCI,SCH MED,DEPT PHARMACOL LOS ANGELES CA 90024
Titolo Testata:
Biochemical pharmacology
fascicolo: 7, volume: 47, anno: 1994,
pagine: 1151 - 1156
SICI:
0006-2952(1994)47:7<1151:TDOM(B>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
LIVER-MICROSOMES; MDMA ECSTASY; RABBIT LIVER; CYTOCHROME-P450; OXIDATION; RAT; (METHYLENEDIOXY)METHAMPHETAMINE; METABOLITES; INHIBITION; MECHANISM;
Keywords:
ECSTASY, METHYLENEDIOXYMETHAMPHETAMINE; DEBRISOQUINE; EXTENSIVE METABOLIZER; POOR METABOLIZER; BRAIN P450; NEUROTOXICITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
31
Recensione:
Indirizzi per estratti:
Citazione:
G.T. Tucker et al., "THE DEMETHYLENATION OF METHYLENEDIOXYMETHAMPHETAMINE (ECSTASY) BY DEBRISOQUINE HYDROXYLASE (CYP2D6)", Biochemical pharmacology, 47(7), 1994, pp. 1151-1156

Abstract

The metabolism of methylenedioxymethamphetamine (MDMA, ''ecstasy'') was examined in a microsomal preparation of the yeast Saccharomyces cerevisiae expressing human debrisoquine hydroxylase, CYP2D6. Only one product, dihydroxymethylamphetamine (DHMA), was detected in the incubation mixture, and this product accounted for all of the substrate consumption at low concentration (10 mu M). Mean +/- SD values of apparent K-m(mu M) and V-max (nmol/min per nmol P450) for the demethylenation of(+) and (-)-MDMA at low concentrations (1-1000 mu M) were 1.72, 0.12 and 6.45, 0.10 and 2.90, 0.10 and 7.61, 0.06, respectively. At high concentrations (>1000 mu M) substrate inhibition was noted, with K-i values of 14.2 and 28.2 mM, respectively, for the (+) and (-) enantiomers. Incubation of MDMA isomers with human liver microsomes indicated that their demethylenation is deficient in the poor metabolizer phenotype. Thus, MDMA is converted to the catecholamine DHMA by CYP2D6, and this may give rise to genetically-determined differences in toxicity.

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Documento generato il 02/04/20 alle ore 06:30:31