The effect of VA-045 on disturbance in consciousness in experimental animal models.

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.