UDK: 615.9:547.785.5:616-092.4
L. I. Bugaeva, E. A. Kuzubova, D. N. Rebrova, M. V. Bukatin, A. A. Spasov
Волгоградский государственный медицинский университет, кафедра фармакологии, кафедра биологии, кафедра фундаментальной медицины и биологии, НИИ фармакологии ВолгГМУ
LD50 values were 1920.96 mg/kg (1858.47÷ 1985.55 mg/kg) for male rats and 2260.3 (2294.69÷ 2226.39) mg/kg for female rats after intragastric administration of toxic doses of RU -185. Based on classification criteria for acute toxicity (GOST 12.1.007-76), we allocated this substance to a moderately toxic drug category. We evaluated functional and behavioral effects of RU-185 on rats and established that its minimum pharmacological activity was observed at a dose of 1.9 mg/kg, while the maximum — at a dose of 59—119 mg/kg. Taking into account the LD50 values and the range of pharmacological activity recorded for RU-185, we calculated the therapeutic index of enoxifol and it equaled 1000. Within the given therapeutic index, the range of pharmacological activity that is safe equals 240, while the range of toxic activity equals 475—1000. We suggest that the data on enoxifol toxicity and the ranges of its pharmacological and toxic activities could be used for dose selection/adjustment in subsequent preclinical toxicity studies.
benzimidazole derivatives, RU-185 (enoxifol), acute toxicity, LD50 limit values, functional and behavioral characteristics of rats.
Букатин Михаил Владимирович — к. м. н., доцент кафедры фундаментальной медицины и биологии, Волгоградский государственный медицинский университет, e-mail: buspak76@mail.ru