Effect of VA-045, a novel apovincaminic acid derivative, on closed head injury-induced neurological dysfunction in aged rats.
Effects of VA-045, a novel apovincaminic acid derivative, on behavioral outcome following closed head injury (CHI) were examined in aged (21-28 months) rats. CHI was induced by dropping a 400 g weight through a tube from 150 cm above a steel helmet placed on the vertex. Beam balancing latency, neurological deficits and body weight were recorded before CHI and for up to 14 days after CHI. When compared with the sham group, all measurements of parameters of behavioral outcome in the CHI group were significantly worsened after CHI. Intraperitoneal administration of VA-045 (1 and 3 mg kg-1) or thyrotropin-releasing hormone (TRH, 10 mg kg-1) and vehicle was started 24 h after CHI, and continued once daily for 13 days. VA-045 but not TRH significantly overcame the CHI-induced neurological deficits, shortened the latency of beam balancing and decreased body weight loss. VA-045 may prove useful for treating aged patients with disturbances of consciousness or motor deficits after CHI.
Okuyama
S
S
Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ohmiya, Saitama, Japan.
Yamada
S
S
Ogawa
S
S
Shima
K
K
Kamata
K
K
Tomisawa
K
K
D000367:Age Factors; D000818:Animals; D001835:Body Weight; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy*; D004195:Disease Models, Animal; D016489:Head Injuries, Closed / Q000150:complications / Q000188:drug therapy*; D008297:Male; D009069:Movement Disorders / Q000175:diagnosis / Q000209:etiology; D009460:Neurologic Examination; D011597:Psychomotor Performance; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*; D014748:Vinca Alkaloids / Q000494:pharmacology*
D014665:Vasodilator Agents; D014748:Vinca Alkaloids; C081044:2-(nitrooxy)ethyl apovincaminate