Onufrienko O. Neurotropic activity of novel 3-acyloxy-1,2-dihydro-3H-1,4-benzodiazepine-2-ones

The thesis is devoted to study of neuropharmacological spectrum of action of 19 novel compounds - 3-acyloxy-1,2-dihydro-1,4-benzodiazepine-2-ones. The study relationships of structure, anticonvulsant, hypnosedative properties of 3-acyloxy-1,2-dihydro-1,4-benzodiazepines showed that the investigated compounds exhibit high anticonvulsant (ED50 0,05-042 mg/kg), hypnotic (ED50 0,22-1,50 mg/kg) and sedative activities (ED50 0,18-0,97 mg/kg) and their pharmacological activity is declining with increasing chain length and lipophilicity. Some of the compounds studied are similar by their pharmacological activites to drug Levanа® ІC and its metabolite 3-hydroxyphenazepam. With chronic administration of cynazepam (0,4 mg/kg) for 14 and 30 days, there is no development of tolerance by the hypnotic effect. In contrast, with chronic administration of 3-hydroxyphenazepam (0,25 mg/kg) for 30 days, the tolerance is developed by the hypnotic effect but sedative activity has been restored. Results obtained on EEG-analysis of influence of 3-hydroxyphenazepam (2,5 mg/kg) on rats' sleep structure were shown that 3-hydroxyphenazepam increased the total sleep time and didn't change the duration of paradoxical sleep. Under the influence of cynazepam and 3-hydroxyphenazepam in rats, injected with reserpine, normal duration of slow wake sleep, as well as paradoxical sleep are increased to the levels of intact rats.