EXPERIMENTS ON THE TOXIC, SEDATIVE AND MUSCLE-RELAXANT POTENCY OF VARIOUS DRUG SOLVENTS IN MICE

The solvents diethyleneglycol monoethylether (Transcutol®), N,N-diethylacetamide, dimethylsulfoxide, glycerine, N-(β-hydroxyethyl)-lactamide, polyethylene glycol 400 (Lutrol 9®), 1,2-propanediol, tetrahydro-furfurylalcohol diethyleneglycolether (Tetraglycol®) and polyoxyethylene sorbitanemonooleate (Tween® 80) were tested in mice for their toxicity, their CNS-profile, their activity in the inclined screen and balance rod tests after i.p. administration as well as for their influence on the hexobarbitone sleeping time and their muscle relaxant properties on the rota-rod after p.o. administration. It is demonstrated that the compounds tested cause a wide variety of pharmacodynamic effects in concentrations in which they are used as drug solvents in the laboratory. As proved by the potentiation of hexobarbitone sleeping time, interactions with the drugs to be tested cannot be excluded. (Just in this test all solvents but three exhibited their highest activity. Only glycerine, N-(β-hydroxymethyl)-lactamide and polyethylene glycol 400 were most potent in the rota-rod test.). So, whenever a drug solvent is used, its concentration must be specified and lack of activity in the respective test system has to be demostrated. Based on their activity in the most sensitive test, the drug solvents examined are recommended not to exceed the following concentrations in drug solutions for screening purpose: diethyleneglycol mono-ethylether 0.7%, N,N-diethylacetamide 0.3%, dimethylsulfoxide 0.9%, glycerine 3.0%, N-(β-hydroxyethyl)-lactamide 50%, polyethylene glycol 400 6.0%, 1,2-propanediol 20%, Tetraglycol® 6.7% and Tween® 80 6.8%. © 1979.