Okuyama S, Imagawa Y, Ogawa S, Saito Y, Araki H, Otomo S, Sakagawa T, Yamada S, Shima K
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Res Commun Chem Pathol Pharmacol. 1993 Oct;82(1):91-100.
The effect of VA-045, a novel apovincaminic acid derivative, on disturbance in consciousness was investigated in mice and rats. VA-045 and thyrotropin-releasing hormone (TRH) shortened the duration of pentobarbital-induced sleeping in rats. VA-045 and TRH improved head impact-induced disturbed behavior in mice. The duration of action of the improving effect of VA-045 was longer than that of TRH. VA-045 and TRH also ameliorated the global cerebral ischemia-induced neurological deficits. Global cerebral ischemia was produced by a 10 min occlusion of both common carotid arteries 24 hr after the permanent electrocauterization of bilateral vertebral arteries. VA-045, but not TRH, attenuated the global cerebral ischemia-induced decreased step through latency (STL) in a passive avoidance task in rats. TRH enhanced spontaneous locomotor activity in mice, whereas VA-045 had no effect on it. The pharmacological effects of VA-045 on disturbance in consciousness will be discussed.
研究了新型阿朴长春胺酸衍生物VA - 045对小鼠和大鼠意识障碍的影响。VA - 045和促甲状腺激素释放激素（TRH）缩短了大鼠戊巴比妥诱导的睡眠时间。VA - 045和TRH改善了小鼠头部撞击诱导的行为障碍。VA - 045改善作用的持续时间比TRH长。VA - 045和TRH还改善了全脑缺血诱导的神经功能缺损。全脑缺血是通过在双侧椎动脉永久性电灼24小时后，阻断双侧颈总动脉10分钟产生的。在大鼠的被动回避任务中，VA - 045而非TRH减轻了全脑缺血诱导的步过潜伏期（STL）缩短。TRH增强了小鼠的自发运动活性，而VA - 045对其无影响。将讨论VA - 045对意识障碍的药理作用。
