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.
Okuyama
S
S
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Imagawa
Y
Y
Ogawa
S
S
Saito
Y
Y
Araki
H
H
Otomo
S
S
Sakagawa
T
T
Yamada
S
S
Shima
K
K
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy; D003243:Consciousness / Q000187:drug effects*; D006259:Craniocerebral Trauma / Q000188:drug therapy; D004195:Disease Models, Animal; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*; D014748:Vinca Alkaloids / Q000494:pharmacology*
D014665:Vasodilator Agents; D014748:Vinca Alkaloids; C081044:2-(nitrooxy)ethyl apovincaminate; D013973:Thyrotropin-Releasing Hormone; D010424:Pentobarbital