Influence of ethanol on the myorelaxant effect of diazepam in rats.
Interaction of ethanol with benzodiazepines can lead to enhanced therapeutic anxyolytic, sedative and hypnotic effects but can also 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) 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 by additional 26 and 46%, respectively, when measured after 15 min. The most pronounced myorelaxation was recorded 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 the 45th min and to 24% at the 105th min after the beginning of the treatment. The results of this preclinical investigation showed that ethanol enhanced the muscle relaxant effect of diazepam in rats. This enhancement as well as duration of the effect was dependent on the applied dose of ethanol.
Bach-Rojecky
Lidija
L
Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia. lbach@pharma.hr
Samarzija
Ita
I
D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005552:Forelimb; D018737:Hand Strength; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D002492:Central Nervous System Depressants; D009125:Muscle Relaxants, Central; D000431:Ethanol; D003975:Diazepam