The Effect of Methamphetamine on Biotransformation of Ethanol: Pilot Study

Abstract

Methamphetamine is one of the most popular recreational drugs in Central Europe and is often combined with ethanol. Various interactions between these two substances have been described including the influence of administered ethanol on biotransformation of methamphetamine. The aim of the present study was to describe the opposite effectthe influence of methamphetamine on biotransformation of ethanol in rats. Methamphetamine was administered for 10 days (10 mg/kg/day) i.p. and ethanol was delivered as an intragastric bolus (2 g/kg) on the10 th day of experiment to both methamphetamine administered rats and control animals. The pharmacokinetic experiment on the whole animal was performed and plasma samples were drawn at the 40 th , 120 th , 210 th and 300 th minute after ethanol administration. Ethanol plasmatic levels reached significantly lower values in the 40 th and 120 th interval when compared to controls. Differences were insignificant in the last two intervals. Our results suggest that chronic methamphetamine administration induces ethanol biotransformation. We suppose that this effect is caused by induction of alcohol dehydrogenase metabolic activity or by allosteric interaction of methamphetamine and this enzyme. More studies have to be conducted to confirm or disprove our hypothesis. Keywords: methamphetamine -ethanol -biotransformation -interaction -rat INTRODUCTIONSubstance abuse is as old as mankind, and brings together health and social problems affecting both the abuser and the society as well. Drugs of abuse are miscellaneous substances eliciting different biologic effects, and their misuse is usually region-specific due to differences in their availability, legislation, and social conditions in the specific area. One of the most popular recreational drugs besides cannabis in the Central Europe DOI 10.2478/v10219-012-0026-4 Brought to you by | Masaryk University et al., 2011). The combination is also more potent in causing memory impairment in rats than administration of single drugs (Yamamura et al., 1992). The molecular mechanism of these behavioural effects is probably carried by different changes on dopamine and serotonin release, which are dependent not only on the substance, but may also vary between rat strains (Nishiguchi et al., 2002, Yamauchi et al., 2000. The chronic administration of METH alone could increase the ET intake in mice because of induction of long term dopaminergic toxicity, and hypodopaminergic state is described to increase the voluntary ET consumption (Gutierrez-Lopez et al., 2010).Preclinical experiments aimed on pharmacokinetic interactions of ET and METH describe the inhibition of METH metabolism when combined with ET (Liang et al., 2012). Increase in the METH plasmatic levels is due to inhibition of METH Ndemethylation and parahydroxylation (Yamada et al., 2001) caused by ET. The similar result was confirmed in humans, too (Shimosato, 1988), whereas other clinical trial with ET and METH combination did not discover any change in METH levels among subjects (Mende...