Acta Pharm. 55 (2005) 115-122

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Short communication  

Influence of ethanol on myorelaxant effect of diazepam in rats


Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Zagreb, HR-10 000 Zagreb, Croatia
Received October 14, 2004      Accepted February 7, 2005

Interaction of ethanol with benzodiazepines can lead to enhanced therapeutic anxyolytic, sedative and hypnotic effect but also can augment unwanted effects such as drowsiness, confusion, amnesia and impaired coordination. In this study we investigated the interaction between ethanol and diazepam and its influence on muscle strength in rats using the grip-strength meter. Three doses of ethanol (0.4, 0.6 and 0.8 g kg-1 of body mass, b.m.) and diazepam (0.75, 1.5 and 7.5 mg kg-1 b.m.) were used in experiments. Single substances and their combinations were tested. The myorelaxant effect of ethanol, measured as grip force (expressed in grams), was dose-dependent. The lowest dose (0.4 g kg-1 b.m.) failed to affect muscle strength while the strongest effect was observed with the highest dose of ethanol (0.8 g kg-1 b.m.) and it lasted for 75 min. Diazepam dose-dependently reduced muscle strength too. However, when ethanol was combined with diazepam (1.5 mg kg-1 b.m.), more enhanced muscle relaxation occurred than by either drug alone. Namely, two lower doses of ethanol (0.4 and 0.6 g kg-1 b.m) enhanced the myorelaxant effect of diazepam for additional 26 and 46%, respectively when measured after 15 min. The myorelaxation was the most pronounced when the highest dose of ethanol (0.8 g kg-1 b.m.) was combined with diazepam: from complete muscle relaxation observed after 15 min, it gradually decreased to 91% at 45th min and to 24% at 105th min after the beginning of the treatment.
The results of this preclinical investigation showed that ethanol enhanced the muscle relaxant effect of diazepam. This enhancement as well as duration of the effect was dependent of the applied dose of ethanol.

Keywords: diazepam, ethanol, interaction, muscle strength