Nishi H, Watanabe T, Mori M
Nihon Yakurigaku Zasshi. 1983 Sep;82(3):191-212.
The effects of suloctidil (MY103) on the central (CNS) and peripheral nervous systems were investigated with single and consecutive administration. The general behavior in mice, awareness and motor activity were slightly depressed with the dose above 300 mg/kg, p.o. of MY 103. Soft stool was also marked in the dose above 100 mg/kg, p.o. in beagles and 1000 mg/kg, p.o. in mice. In beagles, vomiting was another syndrome with 100 and 300 mg/kg, p.o. of MY 103. Spontaneous motor activity was significantly decreased after MY 103 by p.o. administration in the dose above 100 mg/kg in mice and 300 mg/kg in rats. In sleep anesthesia studies, MY 103 and iproniazid did not potentiate the effect of a subthreshold dose of barbital, but those two drugs significantly prolonged the sleeping time of pentobarbital as chlorpromazine did. No anticonvulsive effect was observed with MY 103 in chemo- and electroshock seizure tests. My 103 of 300 mg/kg, p.o. significantly decreased the acetic acid induced writhing number, but no analgesic activity was found in the Haffner's method in mice. In the rotarod test, MY 103 of 30-300 mg/kg, p.o. inhibited the motor coordination dose-dependently. MY 103 antagonized the m-amphetamine group toxicity. A cataleptogenic effect was observed following the relatively high dose of MY 103 by an i.p. route. This effect was antagonized by atropine. The spinal reflexes in the immobilized cat, and spontaneous rabbit EEG were not affected by MY 103. The conditioned avoidance response (CAR) was also not changed with MY 103 in rats. In the isolated phrenic-nerve diaphragm preparation, 10(-4)M MY 103 irreversively inhibited the muscle twitches elicited by nerve and muscle stimulation, but suloctidil at 300 micrograms/kg, i.v., did not suppress the tibialis muscle twitches in vivo. In the consecutive administration study, MY 103 suppressed the CAR in rats and prolonged the thiopental-sleeping time in an administration period-related manner. These changes disappeared rapidly after drug withdrawal. Taking these evidences together, it can be concluded that MY 103 has little effect on the CNS with single administration, but the tendency to depress the CNS was observed after the repeated administration of MY 103.
通过单次给药和连续给药研究了舒洛地尔（MY103）对中枢神经系统（CNS）和外周神经系统的影响。口服MY103剂量高于300mg/kg时，小鼠的一般行为、意识和运动活动略有抑制。口服剂量高于100mg/kg时，比格犬出现软便，小鼠口服剂量高于1000mg/kg时也出现软便。在比格犬中，口服MY103剂量为100和300mg/kg时还出现呕吐症状。小鼠口服剂量高于100mg/kg、大鼠口服剂量高于300mg/kg时，口服MY103后自发运动活动显著降低。在睡眠麻醉研究中，MY103和异烟肼不能增强阈下剂量巴比妥的作用，但这两种药物与氯丙嗪一样能显著延长戊巴比妥的睡眠时间。在化学和电休克惊厥试验中，未观察到MY103的抗惊厥作用。口服300mg/kg的MY103能显著减少醋酸诱导的扭体次数，但在小鼠的哈夫纳法中未发现镇痛活性。在转棒试验中，口服30 - 300mg/kg的MY103剂量依赖性地抑制运动协调。MY103拮抗甲基苯丙胺组的毒性。腹腔注射相对高剂量的MY103后观察到僵住效应，阿托品可拮抗此效应。MY103不影响固定猫的脊髓反射和家兔自发脑电图。大鼠的条件回避反应（CAR）也不受MY103影响。在离体膈神经膈肌标本中，10(-4)M的MY103不可逆地抑制神经和肌肉刺激引起的肌肉抽搐，但静脉注射300μg/kg的舒洛地尔在体内不抑制胫前肌抽搐。在连续给药研究中，MY103抑制大鼠的CAR，并以与给药期相关的方式延长硫喷妥钠睡眠时间。停药后这些变化迅速消失。综合这些证据，可以得出结论，单次给药时MY103对中枢神经系统影响很小，但重复给药后观察到有抑制中枢神经系统的趋势。
