Memantine influences metabolism of dextrometorphan via CYP2D2 in rats
| Autoři | |
|---|---|
| Rok publikování | 2008 |
| Druh | Článek ve sborníku |
| Konference | Regional CINP congress abstracts |
| Fakulta / Pracoviště MU | |
| Citace | |
| Obor | Farmakologie a lékárnická chemie |
| Klíčová slova | memantine; cytochrome P450 |
| Popis | Memantine, an antagonist of NMDA, 5HT3 and some neuronal nicotinic receptors, is used in the treatment of Alzheimer's disease. There are also many other indications for memantine, which are being tested nowadays including depression, opioid dependence, neuropathic pain and others. The aim of our study was to evaluate the influence of memantine on the activity of cytochrome P450 (CYP450). CYP450 is one of the major biotransforming systems in organism and consists of many isoenzymes. The importance of CYP450 in clinical practice is that the huge numbers of drugs are substrates for this enzyme. We have focused on 2D2 rat isoenzyme (equivalent for human 2D6), because of its relation to the metabolism of many psychoactive drugs and clinical possibilities of their co-administration with memantine. The model of isolated perfused rat liver and dextrometorphan specific marker for determination of CYP2D6 activity were used. Memantine was administered to male rats intraperitoneally at the dose of 5 mg/kg/day for 10 days prior to the liver isolation and perfusion. Metabolic transformation of dextrometorphan via CYP2D2 was inhibited in memantine-treated animals. We suggest that a higher risk of adverse effects should be taken in account when memantine is co-administered with drugs metabolized through CYP2D6 pathway. |
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