2008
Memantine influences metabolism of dextrometorphan via CYP2D2 in rats
ZAHRADNÍKOVÁ, Lucia; Ondřej ZENDULKA; Jan JUŘICA; Alexandra ŠULCOVÁ; Eva MCCASKEY HADAŠOVÁ et. al.Základní údaje
Originální název
Memantine influences metabolism of dextrometorphan via CYP2D2 in rats
Název česky
Memantin ovlivňuje metabolizaci dextrometorfanu přes CYP2D2 u potkana
Název anglicky
Memantine influences metabolism of dextrometorphan via CYP2D2 in rats
Autoři
Vydání
Bratislava, Regional CINP congress abstracts, s. 62-62, 2008
Další údaje
Jazyk
čeština
Typ výsledku
Stať ve sborníku
Obor
30104 Pharmacology and pharmacy
Stát vydavatele
Česká republika
Utajení
není předmětem státního či obchodního tajemství
Organizační jednotka
Lékařská fakulta
Klíčová slova anglicky
memantine; cytochrome P450
Štítky
Změněno: 12. 1. 2009 15:28, doc. PharmDr. Ondřej Zendulka, Ph.D.
V originále
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.
Anglicky
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.
Návaznosti
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