Effects of BMY-21502 on Anoxia in Mice

Manabu Amano, Takaaki Hasegawa, Toshitaka Nabeshima, Manabu Amano, Arata Goto, Norimitsu Takahash

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Abstract

The protective effects of BMY-21502 (l-[[l-[2-(trifluoromethyl)-4-pyrimidinyl]-4-piperidinyl]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 1(X) 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.

Original languageEnglish
Pages (from-to)157-163
Number of pages7
JournalThe Japanese Journal of Pharmacology
Volume61
Issue number3
DOIs
Publication statusPublished - 01-01-1993

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All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Amano, M., Hasegawa, T., Nabeshima, T., Amano, M., Goto, A., & Takahash, N. (1993). Effects of BMY-21502 on Anoxia in Mice. The Japanese Journal of Pharmacology, 61(3), 157-163. https://doi.org/10.1254/jjp.61.157