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Titolo:
EFFECT OF CYTOCHROME-P450 2D1 INHIBITION ON HYDROCODONE METABOLISM AND ITS BEHAVIORAL CONSEQUENCES IN RATS
Autore:
TOMKINS DM; OTTON SV; JOHARCHI N; LI NY; BALSTER RF; TYNDALE RF; SELLERS EM;
Indirizzi:
ADDICT RES FDN,BIOBEHAV RES DEPT,33 RUSSELL ST TORONTO ON M5S 2S1 CANADA UNIV TORONTO,DEPT PHARMACOL TORONTO ON CANADA UNIV TORONTO,DEPT MED TORONTO ON CANADA UNIV TORONTO,DEPT PSYCHIAT TORONTO ON CANADA VIRGINIA COMMONWEALTH UNIV,CTR DRUG & ALCOHOL STUDIES RICHMOND VA 00000
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 3, volume: 280, anno: 1997,
pagine: 1374 - 1382
SICI:
0022-3565(1997)280:3<1374:EOC2IO>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEBRISOQUINE 4-HYDROXYLASE; DRUG DISCRIMINATION; HUMAN-LIVER; DA RAT; OXIDATION; CODEINE; INVITRO; QUININE; BRAIN; METHAMPHETAMINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
33
Recensione:
Indirizzi per estratti:
Citazione:
D.M. Tomkins et al., "EFFECT OF CYTOCHROME-P450 2D1 INHIBITION ON HYDROCODONE METABOLISM AND ITS BEHAVIORAL CONSEQUENCES IN RATS", The Journal of pharmacology and experimental therapeutics, 280(3), 1997, pp. 1374-1382

Abstract

Humans that lack cytochrome P450 2D6 (CYP2D6) activity may have an altered risk of drug dependence or abuse because this enzyme is important in the metabolism of some drugs of abuse, including hydrocodone. In rats, hydrocodone conversion to hydromorphone is catalyzed by CYP2D1, the rat homolog of the human CYP2D6. To determine the impact of impaired hydromorphone formation on the behavioral effects of the parent compound, hydrocodone-induced analgesia and hyperactivity, hydrocodone discrimination and self-administration were examined in male Wistar rats, with or without pretreatment with CYP2D1 inhibitors (quinine and budipine). In vivo, quinine (20 mg/kg) and budipine (10 mg/kg) produced amarked suppression in brain and plasma hydromorphone levels detected after the peripheral administration of hydrocodone, thus confirming that the doses used suppressed CYP2D1 activity. In contrast, CYP2D1 inhibition had no impact on the analgesic or discriminative stimulus effects of hydrocodone, nor did this type of manipulation alter hydrocodoneself-administration. The effects of quinine on the locomotor activating effects of hydrocodone were subtle at best, Because inhibition of CYP2D1 in this rat strain is proposed to be a useful animal counterpartfor studying the impact of CYP2D6 polymorphism in humans, these data suggest that differences in CYP2D6 phenotype will have limited influence on the drug response to hydrocodone after nonoral administration. This has recently been verified in a study showing that inhibition of hydrocodone biotransformation to hydromorphone does not affect measuresof abuse liability. Therefore, hydrocodone's behavioral effects are most likely attributable to its own intrinsic effects at mu opioid receptors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 15:30:17