Publication details
VPLYV METANANDAMIDU NA AKTIVITU CYTOCHRÓMU P450 AKO PREDIKČNÉHO FAKTORU TOXICITY XENOBIOTÍK
| Title in English | THE INFLUENCE OF METHANANDAMIDE AND SEX ON THE ACTIVITY OF CYTOCHROME P 450 AS A PREDICTIVE FACTOR OF XENOBIOTICS TOXICITY |
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| Authors | |
| Year of publication | 2007 |
| Type | Article in Proceedings |
| Conference | Sborník abstrakt, 12. Mezioborová česko-slovenská toxikologická konference |
| MU Faculty or unit | |
| Citation | |
| Field | Pharmacology and pharmaceutical chemistry |
| Keywords | cytochrome P450; gender differencies; isolated perfused liver |
| Description | Cannabinoids have a long history of consumption for recreational and medicinal reasons. The primary active constituent of the hemp plant Cannabis sativa is 9-tetrahydrocannabinol (THC)1. In humans, psychoactive cannabinoids produce euphoria, enhancement of sensory perception, tachycardia, antinociception, difficulties in concentration and impairment of memory. Researchers in the 1970s, 80s, and 90s primarily assessed cannabis ability to temporarily alleviate various disease symptoms, such as the nausea associated with cancer chemotherapy. Of particular interest, scientists are investigating cannabinoid capacity to moderate autoimmune disorders, such as multiple sclerosis, rheumatoid arthritis and inflammatory bowel disease, as well as their role in the treatment of neurological disorders such as Alzheimer's disease and amyotrophic lateral sclerosis. Anandamide, an endogenous ligand for brain cannabinoid CB1 receptor, produces many behavioural effects similar to those of THC, the main psychoactive ingredient in marijuana2. (R)-(+)-methanandamide is a synthetic long-lasting arachidonylethanolamide (anandamide) analogue that is metabolically stable and displays higher affinity for the cannabinoid receptor. The enzymatic system of cytochrome P 450 (CYP450) is part of phase I of enzymatic biotransformation. It consists of many isoenzymes characterized by specific substrates and organ localization. These isoenzymes are most predominant in the liver, but can also be found in the intestine, lungs and other organs3. Among the diverse human genes, several have been identified to be particularly important in oxidative metabolism. They are: CYP3A4 (by far the most important), CYP2D6 (is responsible for the metabolism of many psychotherapeutic agents), CYP 2C6 and CYP2C19. CYP450 is involved in metabolism of many endogenous as well as exogenous substrates. Both, the induction and inhibition of specific CYP450 isoenzymes are important in terms of the efficacy or toxicity of drugs that are substrates for this system3. Interindividual variability of activity of oxidative and conjugating enzymes, especially the system of CYP450, can be based on many exogenous as well as endogenous influences e.g. sex, age, genetic factors or interactions between simultaneously applied drugs. The tendency to adapt the dosage of drug for the particular patient and to individualize and optimise the therapy to prevent adverse effects, to decrease the duration and costs of therapy is often seen in modern pharmacotherapy. One of the number of possible influences of drug metabolism which is frequently missed out is sex. CYP450 metabolizes many drugs including THC, the major psychoactive cannabinoid present in marijuana. The aim of this work was to investigate the effect of repeated administration of (R)-(+)-methanandamide on rat liver CYP2D2 isoenzyme using dextromethorphan (DEM) as a specific marker4. We have also studied the role of sex on the activity of CYP2D2 isoenzyme. |
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