Kamioka T, Sakai Y
Nihon Yakurigaku Zasshi. 1980 Sep;76(6):533-47.
Behavioral pharmacological properties of mianserin (1,2,3,4,10,14b-hexahydro-2-methyldibenzol[c,f]pyrazino [1.2-a]azepine monohydrochloride) were investigated in comparison with imipramine (IMP) and amitriptyline (ATP). Mianserin antagonized reserpine-induced hypothermia but to a much lesser extent than IMP or ATP, and did not block the ptosis evoked by reserpine or tetrabenazine. Amphetamine-induced stereotyped behavior was significantly enhanced by both IMP and ATP, but not by mianserin. Unlike IMP or ATP, haloperidol-induced catalepsy in the rat was not blocked by mianserin. Like IMP or ATP, mianserin did not suppress the convulsions induced by bemegride or strychnine in the mouse, and or emetic action of apomorphine in the dog, while only mianserin did not block the convulsions evoked by electric shocks. Mianserin more strongly potentiated the anesthetic action of thiopental than did IMP. ATP showed strong muscle relaxant action and the impairment of coordinated motor activities both in mice and rats, in the inclinated screen test and rotarod test, while, like IMP, these actions of mianserin were significant only in the rat. Catalepsy was not induced nor was the righting reflex suppressed by mianserin. In the low spinal cat, mianserin did not depress the amplitude of extensor MSR. Moreover, the MSR inhibition induced by conditioning stimulation of ipsilateral cutaneous afferents and the MSR potentiation evoked by conditioning stimulation of contralateral saphenous nerve were unaffected by mianserin. The curious behavior of mice and rats was significantly and dose-dependently suppressed by mianserin, and tended to be suppressed by ATP, while an enhancement was seen with IMP in large doses. Mianserin was the most potent in suppressing the fighting behavior induced by long-term isolation of the mouse, and was the weakest in suppressing electric-stimulation-induced fighting behavior, compared with IMP and ATP. Mianserin showed no significant suppression of the muricide behavior of the olfactory bulbectomized rat, while IMP significantly suppressed it. No significant differences were observed among mianserin, IMP and ATP as to their actions on the conflict behavior and the shuttle-box type conditioned avoidance behavior of the rat. These results indicate that behavioral pharmacological actions of mianserin were not always the same as those of IMP and ATP. Therefore, mianserin may be a new antidepressant with mechanisms of action which differ from that of the usual tricyclic antidepressants.
将米安色林(1,2,3,4,10,14b - 六氢 - 2 - 甲基二苯并[c,f]吡嗪并[1.2 - a]氮杂卓盐酸盐)的行为药理学特性与丙咪嗪(IMP)和阿米替林(ATP)进行了比较研究。米安色林可拮抗利血平诱导的体温过低,但程度远低于IMP或ATP,且不阻断利血平或丁苯那嗪诱发的眼睑下垂。IMP和ATP均可显著增强苯丙胺诱导的刻板行为,但米安色林无此作用。与IMP或ATP不同,米安色林不阻断氟哌啶醇诱导的大鼠僵住症。与IMP或ATP一样,米安色林不抑制美解眠或士的宁在小鼠中诱发的惊厥,也不抑制阿扑吗啡在犬中的催吐作用,而只有米安色林不阻断电击诱发的惊厥。米安色林比IMP更强烈地增强硫喷妥钠的麻醉作用。ATP在倾斜屏幕试验和转棒试验中对小鼠和大鼠均表现出强烈的肌肉松弛作用以及对协调运动活动的损害,而米安色林与IMP一样仅在大鼠中这些作用显著。米安色林既不诱发僵住症也不抑制翻正反射。在低位脊髓猫中,米安色林不降低伸肌的单突触反射(MSR)幅度。此外,米安色林不影响同侧皮肤传入神经条件刺激诱导的MSR抑制以及对侧隐神经条件刺激诱发的MSR增强。米安色林可显著且剂量依赖性地抑制小鼠和大鼠的好奇行为,ATP有抑制趋势,而大剂量IMP则使其增强。与IMP和ATP相比,米安色林在抑制长期隔离小鼠诱发的攻击行为方面最有效,而在抑制电刺激诱发的攻击行为方面最弱。米安色林对嗅球切除大鼠的杀鼠行为无显著抑制作用,而IMP则有显著抑制作用。在对大鼠的冲突行为和穿梭箱型条件回避行为的作用方面,米安色林、IMP和ATP之间未观察到显著差异。这些结果表明,米安色林的行为药理学作用并不总是与IMP和ATP相同。因此,米安色林可能是一种作用机制与常用三环类抗抑郁药不同的新型抗抑郁药。