Takai A, Hirai S, Watanabe I, Hiraiwa T, Abe N, Arai H, Omori M, Tanada K, Senda N, Hashiba K, Matsukura K, Takata K, Okami H
Jpn J Antibiot. 1982 Sep;35(9):2139-54.
General pharmacological studies on T-1982 produced the following results. On central nervous system, subcutaneous injection of T-1982 at dose of 2,000 mg/kg hastened the onset of pentetrazole-induced tonic extensor in mice. T-1982 had no effect on spontaneous motor activity, pentobarbital hypnosis, body temperature or EEG in mice or rabbits, and also did not show motor incoordinate, anticonvulsive or analgesic activity in mice at intravenous doses of 250--1,000 mg/kg or subcutaneous doses of 500--2,000 mg/kg. On motor and sensory nervous systems, no effect of T-1982 was noted on spinal reflex, neuromuscular junction, conduction anesthesia or surface anesthesia in rats or rabbits. On respiratory, cardiovascular and autonomic nervous systems, T-1982 caused transient increase of respiratory rate, slight hypotension and transient increase of femoral blood flow in dogs at intravenous doses of 250--1,000 mg/kg. However, it caused a slight hypertensive tendency in rabbits. Heart rate and ECG in dogs or rabbits, blood pressure response to epinephrine, isoproterenol, acetylcholine or histamine in dogs, nictitating membrane in cats and pupil size in mice were not affected after intravenous injection of T-1982. No effect was found on isolated guinea pig atrium or rabbit descending aorta following T-1982 application. On renal function in rats, T-1982 caused an increase of PSP excretion but had no effect on urine volume or electrolytes excretion at intravenous doses of 250--1,000 mg/kg. T-1982 prolonged bleeding time in mice at intravenous doses of 500--1,000 mg/kg, but did not show hemolytic property and inhibitory activity on blood coagulation or platelet aggregation in vitro experiments. Spontaneous movement and tone of isolated stomach, ileum, colon, uterus, vas deferens or trachea and acetylcholine-, histamine-, nicotine- or barium chloride-induced contraction of ileum were not affected following T-1982 application. Intestinal propulsion of barium meal in mice, gastric secretion and carrageenin-induced edema in rats were not affected after intravenous injection of T-1982. T-1982 increased bile secretion in rats dose-dependently at intravenous doses of 31.3--125 mg/kg. The local irritative activity of T-1982 in rats was slightly milder than cefoxitin and moderately milder than cefmetazole after intradermal injection. In conclusion, these results suggest that T-1982 would not cause any adverse effects at its estimated clinical doses of 10--20 mg/kg (500--1,000 mg/man).
对T - 1982进行的一般药理学研究产生了以下结果。在中枢神经系统方面，以2000mg/kg的剂量皮下注射T - 1982可加速小鼠戊四氮诱导的强直性伸展发作。T - 1982对小鼠或兔子的自发运动活动、戊巴比妥催眠、体温或脑电图没有影响，并且在静脉注射剂量为250 - 1000mg/kg或皮下注射剂量为500 - 2000mg/kg时，对小鼠也未表现出运动不协调、抗惊厥或镇痛活性。在运动和感觉神经系统方面，未观察到T - 1982对大鼠或兔子的脊髓反射、神经肌肉接头、传导麻醉或表面麻醉有影响。在呼吸、心血管和自主神经系统方面，在静脉注射剂量为250 - 1000mg/kg时，T - 1982可使犬的呼吸频率短暂增加、轻度低血压和股血流量短暂增加。然而，它在兔子中引起轻微的高血压倾向。静脉注射T - 1982后，犬或兔子的心率和心电图、犬对肾上腺素、异丙肾上腺素、乙酰胆碱或组胺的血压反应、猫的瞬膜和小鼠的瞳孔大小均未受影响。应用T - 1982后，对离体豚鼠心房或兔降主动脉没有影响。在大鼠的肾功能方面，在静脉注射剂量为250 - 1000mg/kg时，T - 1982可使PSP排泄增加，但对尿量或电解质排泄没有影响。在静脉注射剂量为500 - 1000mg/kg时，T - 1982可延长小鼠的出血时间，但在体外实验中未表现出溶血特性以及对血液凝固或血小板聚集的抑制活性。应用T - 1982后，离体胃、回肠、结肠、子宫、输精管或气管的自发运动和张力以及乙酰胆碱、组胺、尼古丁或氯化钡诱导的回肠收缩均未受影响。静脉注射T - 1982后，小鼠的钡餐肠道推进、大鼠的胃液分泌和角叉菜胶诱导的水肿均未受影响。在静脉注射剂量为31.3 - 125mg/kg时，T - 1982可使大鼠胆汁分泌呈剂量依赖性增加。皮内注射后，T - 1982在大鼠中的局部刺激活性略轻于头孢西丁，中度轻于头孢美唑。总之，这些结果表明，在估计的临床剂量10 - 20mg/kg（500 - 1000mg/人）下，T - 1982不会引起任何不良反应。
