Effects of BMY-21502 on Anoxia in Mice

The Japanese Journal of Pharmacology

Manabu Amano¹  Arata Goto²  Takaaki Hasegawa¹  Norimitsu Takahashi²  Toshitaka Nabeshima¹ 

[1] Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine;Pharmacology Laboratory, Preclinical Research Laboratories, Bristol-Myers Squibb K.K.

关键词: Anti-anoxic effect;    BMY-21502;    Oxiracetam;    Idebenone;   

DOI  :  10.1254/jjp.61.157

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(34)Cited-By(4)The protective effects of BMY-21502 (1-[[1-[2-(trifluoromethyl)-4-pyrimidinyl]-4piperidinyl]methyl]-2-pyrrolidinone)against cerebral anoxia were investigated using various models in mice, in comparison with those of other cerebroactive drugs. Oral administration of BMY-21502 (10-100 mg/kg)significantly prolonged the survival time in KCN (2.4 mg/kg, i.v.)-induced anoxia. Oxiracetam and idebenone exerted similar but weak protection at doses above 100 mg/kg, p.o. and only at a dose of 100 mg/kg, p.o., respectively. Significant protection by BMY-21502 against moderate hypobaric hypoxia was observed at doses of 30 and 100 mg/kg, p.o. Idebenone (100 and 300 mg/kg, p.o.)significantly prolonged the survival time of mice in this model, but oxiracetam (30-300 mg/kg, p.o.)did not. Oral administration of all of these drugs (BMY-21502, 3 300 mg/kg; Oxiracetam, 100-1000 mg/kg; Idebenone, 100-1000 mg/kg)failed to increase the number of gasps and the duration of gasping in the decapitated head of mice as a complete ischemic model. The anti-anoxic effect of BMY-21502 in the KCN-anoxia model was blocked by pretreatment with scopolamine. These findings suggest that BMY-21502 has an anti-anoxic action superior to those of the other cerebroactive drugs used, and activation of the CNS cholinergic system is involved as one of the causative mechanisms for the anti-anoxic effect of BMY-21502.

【 授权许可】

Unknown