Influence of ethanol on myorelaxant effect of diazepam in rats

Konzumacija etanola može dovesti do pojačanog anksiolitičkog, sedativnog i hipnotskog djelovanja benzodiazepina, a može i pojačati njihove neželjene reakcije, kao što su vrtoglavica, konfuzija, amnezija i poremećena koordinacija. Cilj ovog rada bio je ispitati miorelaksirajući učinak diazepama i etanola kod štakora koristeći »metodu jačine stiska«. Također se željelo utvrditi u kojoj dozi te u kolikoj mjeri primjena etanola može pojačati djelovanje diazepama. Stoga su u ispitivanja korištene tri doze etanola (0.4, 0.6, i 0.8 g kg-1 tjelesne mase, t.m.) i diazepama (0.75, 1.5, i 7.5 mg kg-1 t.m.). Miorelaksirajuće je djelovanje ispitivano nakon jednokratne primjene obje supstance pojedinačno kao i u njihovoj kombinaciji. Miorelaksirajući učinak etanola kao i diazepama pojedinačno bio je ovisan o dozi. Što je doza bila veća, to je učinak bio jači, a vrijeme njegova trajanja bilo je dulje. Kod istodobne primjene diazepama (1.5 mg kg-1 t.m.) s različitim dozama etanola, miorelaksirajuće se djelovanje značajno pojačalo i produljilo u odnosu na ispitivane supstance pojedinačno. Pritom je učinak bio najjače izražen u prvih 15 min, a potom je postupno slabio. Naime, u tom je vremenu najmanja doza etanola korištena u ovom radu pojačala miorelaksirajuće djelovanje diazepama za dodatnih 26%, srednja za čak 46% dok je u kombinaciji s najvećom dozom etanola nastupila potpuna mišićna relaksacija koja je postupno, tijekom vremena, slabila da bi 105 min nakon primjene supstancija iznosila 24%. Stoga rezultati ovog pretkliničkog ispitivanja pokazuju da etanol, ovisno o dozi, pojačava miorelaksirajuće djelovanje diazepama kod eksperimentalnih životinja. Ono je trajalo dulje što je doza etanola u kombinaciji s diazepamom bila veća.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