Effect of VA-045 on a closed head injury model in rats.
The effect of VA-045, a novel apovincaminic acid derivative, was studied in a model of closed head injury (CHI) in rats. CHI was induced by dropping a 400 g weight through a tube from 70 cm above a steel helmet placed on the vertex. Intravenous administration of VA-045 and thyrotropin-releasing hormone (TRH) reduced both the duration of loss of righting reflex and the duration of disruption of spontaneous movement caused by CHI. VA-045, but not TRH attenuated the CHI-induced decreased step through latency (STL) on a passive avoidance task. Over the same time schedule, however, VA-045 did not attenuate the scopolamine-induced decreased STL. CHI-induced reduction of the amplitude of somatosensory evoked potentials (SEP) was recovered by VA-045 but not by TRH. These findings indicate that VA-045 may be useful for treating patients with CHI-induced disturbance in consciousness.
Okuyama
S
S
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Imagawa
Y
Y
Ogawa
S
S
Araki
H
H
Otomo
S
S
Sakagawa
T
T
Yamada
S
S
Shima
K
K
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D003243:Consciousness / Q000187:drug effects; D006259:Craniocerebral Trauma / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013345:Subarachnoid Hemorrhage / Q000209:etiology; 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