Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Mosul, P.O. Box 11136, Mosul, Iraq.
Environ Toxicol Pharmacol. 1999 Apr;7(2):119-25. doi: 10.1016/s1382-6689(99)00002-2.
The efficacy of diphenhydramine in the prevention and treatment of methomyl-induced toxicosis was evaluated in female rats. Diphenhydramine at 10 and 20 mg/kg subcutaneously (s.c.) given immediately after methomyl increased the LD(50) of methomyl (6.29 mg/kg intraperitoneally (i.p.)) in the rats by 71 and 75% respectively. Diphenhydramine at 20 mg/kg s.c. given immediately after methomyl (6 mg/kg i.p.) decreased the occurrence of cholinergic signs of toxicosis, and prevented convulsions, gasping and death by 100% in comparison with the control (methomyl-saline) group. Diphenhydramine administration at 2.5, 5 and 10 mg/kg s.c. 20 min before methomyl (8 mg/kg i.p.) significantly and dose-dependently decreased the number of convulsion episodes in rats in comparison with the control group. This effect was similar to those of atropine and diazepam pretreatments at 20 mg/kg s.c. Diphenhydramine and atropine at 20 mg/kg i.p. given 5 min after the methomyl administration (8 mg/kg i.p.) were close to each other in reducing the signs of cholinergic toxicity as well as the severity of toxicosis induced by methomyl in rats. Methomyl at 4 and 8 mg/kg i.p. significantly decreased erythrocyte (40 and 43%) and plasma (23 and 31%) cholinesterase activities in comparison with the control group. Diphenhydramine (10 mg/kg s.c.) injected 15 min before methomyl significantly decreased the inhibitory effect of methomyl (4 and 8 mg/kg i.p.) on erythrocyte cholinesterase to 17 and 27%, respectively. The inhibitory effect on plasma cholinesterase was not affected by the diphenhydramine pretreatment. The data suggest that diphenhydramine could be of therapeutic value in reducing the toxic effects of methomyl.
苯海拉明预防和治疗灭多威诱导的中毒的疗效在雌性大鼠中进行了评估。苯海拉明以 10 和 20 mg/kg 皮下（s.c.）给药，在灭多威（6.29 mg/kg 腹腔内（i.p.））给药后立即增加大鼠的 LD（50）分别增加了 71%和 75%。苯海拉明以 20 mg/kg s.c. 给药，在灭多威（6 mg/kg i.p.）后立即给药，与对照组（灭多威-生理盐水）相比，100%降低了毒蕈碱样体征的发生，并防止了惊厥、喘息和死亡。苯海拉明以 2.5、5 和 10 mg/kg s.c. 给药，在灭多威（8 mg/kg i.p.）前 20 分钟给药，与对照组相比，显著且剂量依赖性地减少了大鼠惊厥发作的次数。这种作用与阿托品和地西泮预处理 20 mg/kg s.c. 相似。苯海拉明和阿托品以 20 mg/kg i.p. 给药，在灭多威给药后 5 分钟（8 mg/kg i.p.）给药，在减少大鼠胆碱能毒性的体征以及灭多威诱导的中毒的严重程度方面彼此接近。灭多威以 4 和 8 mg/kg i.p. 给药，与对照组相比，显著降低了红细胞（40%和 43%）和血浆（23%和 31%）胆碱酯酶活性。苯海拉明（10 mg/kg s.c.）在灭多威前 15 分钟给药，显著降低了灭多威（4 和 8 mg/kg i.p.）对红细胞胆碱酯酶的抑制作用，分别为 17%和 27%。苯海拉明预处理对血浆胆碱酯酶的抑制作用没有影响。数据表明，苯海拉明可能具有治疗价值，可降低灭多威的毒性作用。
