P02-238 - Neurotropic Activity of Aminoalcohols Based on Glycidylcamphorimide

Abstract

The present work deals with neurotropic activity of three novel aminoalcohols C-81, C-78 and C-115, synthesized from glycidylcamphorimide, exo- and endo-aminomethylnorbornenes and aminoethyladamantan (remantadin). Experiments have been carried out on both genders adult white mice at the dozes of 1/10 LD50. Acute toxicity of compounds (LD50) has been measured by Litchfield & Wilcoxon method in Prozorovsky V.B. modification and amounts 803 – 1196 mg/kg for C-81, C-78 respectiverly (they are considerably less toxic than exo- and endo-aminomethylnorbornenes, LD50 for which amounts 335 and 331 mg/kg). The most toxic compound is aminoalcohol C-115 with adamantane fragment (LD50 370 mg/kg). Investigation of analgesic activity has been carried out by determination of pain threshold by thermal irritation method (hot plate) at 55°C. Anticonvulsive activity has been studied by corazole spasm test. Tranquilizing activity of preparations was studied by the test of barbituric sleep duration increase caused by hexenale prepared ex tempore (60 mg/kg). Antihypoxic activity was investigated using the closed space model by mice lifetime duration. The activity has been calculated in percentage in relation to control group of animals. All aminoalcohols by all types of activity essentially surpass initial amines. For exo-aminoalcohol C-81 the most intense activities are analgesic (+195.0%) and tranquilizing (+102.3%), and for endo-isomer C-78 - anticonvulsive activity (+213.3%). Levels of antihypoxic effect of aminoalcohols C-115, C-81 and C-78 amount 16.0, 42.0 and 47.5% accordingly. Compound C-115 shows medium analgesic activity (67.1%), and on all other parameters considerably concedes aminoalcohols with a norbornene fragment.