Publication details

THE INFLUENCE OF CANNABINOID METHANANDAMIDE ON THE ACTIVITY OF HEPATIC CYP2D2 IN RATS

Authors

ZAHRADNÍKOVÁ Lucia ZENDULKA Ondřej JUŘICA Jan MCCASKEY HADAŠOVÁ Eva

Year of publication 2007
Type Article in Periodical
Magazine / Source Biomedical Papers
MU Faculty or unit

Faculty of Medicine

Citation
Field Pharmacology and pharmaceutical chemistry
Keywords (R)-(+)-Methanandamide/ CYP 2D2/ isolated perfused rat liver
Description Anandamide, an endogenous ligand for brain cannabinoid CB1 receptor, produces many behavioral effects similar to those of 9-tetrahydrocannabinol (THC), the main psychoactive ingredient in marijuana. (R)-(+)-methanandamide (MET) is a synthetic long-lasting arachidonylethanolamide (anandamide) analog that is metabolically stable and displays higher affinity for the cannabinoid receptor. The aim of this work was to investigate the effect of repeated administration of MET on cytochrome P450 (CYP450) mediated biotransformation in rat. The enzymatic system of CYP450 is a part of phase I of enzymatic biotransformation. CYP450 metabolizes many drugs including the major psychoactive cannabinoid present in marijuana THC. We have studied the influence of (R)-(+)-methanandamide on rat liver CYP2D2 isoenzyme using dextromethorphan as a specific marker. As we expected, the activity of CYP2D2 differed due to pretreatment with methanandamide. In our experiments the influence of this compound on rat CYP2D2 was inhibitive and metabolic activity of studied isoenzyme CYP2D2 in male rats was significantly higher in the control group than in (R)-(+)-methanandamide group.
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