sm-346 and Alcoholism

Effect of trimetazidine (20 and 30 mg/kg) on elevated plus maze behavior of rodents was assessed in the genetic and pharmacological anxiety models. Single intraperitoneal injection of trimetazidine in a dose of 20 mg/kg prevented anxiety development in highly emotional male BALB/c mice and increased the time spent in open arms of the maze. In outbred male rats receiving 10% ethanol solution for 20 weeks, trimetazidine administered intraperitoneally in a dose of 20 mg/kg for 28 days abolished ethanol withdrawal-induced anxiogenesis developed against the background of 4-week alcohol deprivation: it increased the time spent in open arms, the number of entries into open arms, and total locomotor activity in the maze. Anxiolytic properties of trimetazidine were not inferior to those of the non-benzodiazepine anxiolytic Afobazole (fabomotizole) in acute and chronic administration.

Topics: Alcoholism; Animals; Animals, Outbred Strains; Anti-Anxiety Agents; Anxiety; Benzimidazoles; Drug Evaluation, Preclinical; Ethanol; Male; Mice, Inbred BALB C; Morpholines; Rats; Substance Withdrawal Syndrome; Trimetazidine

Prenatal ethanol leads to the formation of a wide spectrum of neurotoxic injuries to the brain in embryos by day 20 of intrauterine development. High levels of DNA aberrations and apoptotic comets were detected in tissues of 13-day embryos and placentas of rats receiving 40% ethanol orally (4 ml/kg) during gestation. The increase in the levels of DNA aberrations and apoptotic comets in the embryonic and placental tissues of alcoholic rats on day 13 of gestation correlated with the emergence of morphological abnormalities of the brain in the embryos on day 20 of intrauterine development. Afobazole (antimutagen) in doses of 1 and 10 mg/kg reduced the genotoxic effects of ethanol in embryonic and placental tissues and the relevant neurotoxic involvement of the brain.

Topics: Alcoholism; Animals; Animals, Outbred Strains; Apoptosis; Benzimidazoles; Brain; Comet Assay; DNA Damage; Embryo, Mammalian; Ethanol; Female; Morpholines; Pregnancy; Prenatal Exposure Delayed Effects; Protective Agents; Rats