抗抑郁剂吗氯贝胺的行为效应

Behavioral effects of the antidepressant moclobemide

加强５－羟色氨酸及β－苯乙胺致小鼠刻板行为实验表明，ｉｇ吗氯贝胺（Ｍｏｃ）对单胺氧化酶（ＭＡＯ）－Ａ的选择性抑制作用（ＥＤ５０＝０．３３ｍｇｋｇ－１，２ｈ）较ＭＡＯ－Ｂ（ＥＤ５０＝１２．７ｍｇｋｇ－１，２ｈ）强约３９倍．２４ｈ内ｉｐＭｏｃ３００ｍｇｋｇ－１有一定镇静作用．对运动系统无明显影响，不引起记忆及定向障碍．Ｍｏｃ６００ｍｇｋｇ－１不能对抗氧化震颤素引起的小鼠震颤和分泌增加．Ｍｏｃ的ＬＤ５０为小鼠：１．３－１．５ｇｋｇ－１ｉｇ；１９８－１９９ｍｇｋｇ－１ｉｖ；大鼠：５４１－５６２ｍｇｋｇ－１ｉｐ．Ｍｏｃ剂量依赖地对抗利血平引起的小鼠和大鼠睑下垂，活动减少和体温降低；使慢性应激刺激引起的小鼠活动性增高及穿箱逃避电击反应失败率增高得到恢复，提示其抗抑郁作用．

The pharmacological effects and toxicity of moclobemide hydrochloride (Moc), a reversible and selective inhibitor of monoamine oxidase A (MAO A), were observed. From potentiation of 5 hydroxy L tryptophan and β phenylethylamine induced stereotyped behavior in mice it was shown that the selectivity of Moc was as about 39 times high for MAO A (ED 50 =0.33 mg·kg 1 , 2 h) as for MAO B (ED 50 =12.7 mg·kg 1 , 2 h). At 300 mg·kg 1 within 24 h, Moc decreased spontaneous motor activity in rats, but had no effect on holding a wire with forepaws, staying on a rotarod and the performance in maze test. Moc 600 mg·kg 1 couldn′t antagonize the oxotremorine induced tremor in mice. LD 50 values of Moc were 1.3-1.5 g·kg 1 ig, 198-199 mg·kg 1 iv (mice) and 541-562 mg·kg 1 ip (rats) with no significant difference between ♂ and ♀. Moc was active in 2 experimental models predicting antidepressant activity. 1) It prevented dose dependently ptosis, akinesia and hypothermia induced by reserpine in mice and rats. 2) It restored the shuttle box deficits induced by 9 d unpredictable stresses in mice.