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Titolo:
Inhibition of cytochrome P450 2D6 modifies codeine abuse liability
Autore:
Kathiramalainathan, K; Kaplan, HL; Romach, MK; Busto, UE; Li, NY; Sawe, J; Tyndale, RF; Sellers, EM;
Indirizzi:
Univ Toronto, Dept Pharmacol, Toronto, ON, Canada Univ Toronto Toronto ONCanada onto, Dept Pharmacol, Toronto, ON, Canada Univ Toronto, Dept Med, Toronto, ON, Canada Univ Toronto Toronto ON Canada iv Toronto, Dept Med, Toronto, ON, Canada Univ Toronto, Dept Psychiat, Toronto, ON, Canada Univ Toronto Toronto ON Canada ronto, Dept Psychiat, Toronto, ON, Canada Univ Toronto, Fac Pharm, Toronto, ON, Canada Univ Toronto Toronto ON Canada v Toronto, Fac Pharm, Toronto, ON, Canada Sunnybrook & Womens Coll, Ctr Res Womens Hlth, Psychopharmacol & Dependence Res Unit, Toronto, ON M5S 1B2, Canada Sunnybrook & Womens Coll Toronto ON Canada M5S 1B2 to, ON M5S 1B2, Canada Ctr Addict & Mental Hlth, Toronto, ON, Canada Ctr Addict & Mental Hlth Toronto ON Canada tal Hlth, Toronto, ON, Canada Karolinska Inst, Huddinge, Sweden Karolinska Inst Huddinge SwedenKarolinska Inst, Huddinge, Sweden Huddinge Univ Hosp, S-14186 Huddinge, Sweden Huddinge Univ Hosp HuddingeSweden S-14186 osp, S-14186 Huddinge, Sweden
Titolo Testata:
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
fascicolo: 4, volume: 20, anno: 2000,
pagine: 435 - 444
SICI:
0271-0749(200008)20:4<435:IOCP2M>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERFORMANCE LIQUID-CHROMATOGRAPHY; POOR METABOLIZERS; MORPHINE; DEBRISOQUINE; SPARTEINE; HUMANS; CYP2D6; DEXTROMETHORPHAN; PHARMACOKINETICS; ALPRAZOLAM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Sellers, EM Sunnybrook & Womens Coll, Hlth Sci Ctr, Psychopharmacol & Dependence Res Unit, Womens Coll Campus,76 Grenville St, Toronto, ON M5S 1B2, Canada Sunnybrook & Womens Coll Womens Coll Campus,76 Grenville St Toronto ON Canada M5S 1B2
Citazione:
K. Kathiramalainathan et al., "Inhibition of cytochrome P450 2D6 modifies codeine abuse liability", J CL PSYCH, 20(4), 2000, pp. 435-444

Abstract

Oral codeine preparations, widely used for analgesia and cough suppression, are abused by some individuals for their mood-altering properties. The enzymatic O-demethylation of codeine is catalyzed by cytochrome P450 2D6 (CYP2D6), leading to the production of metabolites (morphine, morphine-6-glucuronide) that are pharmacologically more potent than codeine. A placebo-controlled, single-blind study was conducted to characterize the subjective effects of codeine associated with abuse liability and to determine the importance of metabolic O-demethylation to codeine abuse liability. Twelve non-drug-dependent subjects received oral administration of placebo and codeine 60, 120, and 180 mg, and a favorite dose CFD) was determined for each subject. The FD was readministered after pretreatment with placebo, 50 mg of quinidine (a specific, selective CYP2D6 inhibitor) once, or 50 mg of quinidine given four times a day for 4 days. Single-dose quinidine pretreatment significantly decreased the recovery of O-demethylated metabolites in plasma (p <0.01) and resulted in a decrease in the positive (e.g., "high," p < 0.05) and negative (e.g., nausea, p < 0.05) subjective effects of codeine in boththe FD120 and FD180 groups. Short-term quinidine pretreatment inhibited codeine O-demethyiation more than did single-dose quinidine pretreatment (p <0.01), and it decreased positive codeine effects in the FD120 group (N = 7), but unexpectedly not in the FD180 group (N = 5). These results suggest that the O-demethylated metabolites contribute substantially to the subjective effects and abuse liability of codeine.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/01/20 alle ore 00:48:55