Effects of BMY-21502 on anoxia in mice.
The protective effects of BMY-21502 (1-[[1-[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 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.
Amano
M
M
Department of Neuropsychopharmacology, Nagoya University School of Medicine, Japan.
Goto
A
A
Takahashi
N
N
Hasegawa
T
T
Nabeshima
T
T
D000818:Animals; D001274:Atmospheric Pressure; D016227:Benzoquinones / Q000627:therapeutic use; D002545:Brain Ischemia / Q000517:prevention & control; D004195:Disease Models, Animal; D002534:Hypoxia, Brain / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D011190:Potassium Cyanide; D011619:Psychotropic Drugs / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D011759:Pyrrolidines / Q000627:therapeutic use; D011760:Pyrrolidinones / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D012601:Scopolamine / Q000494:pharmacology; D014451:Ubiquinone / Q000031:analogs & derivatives
D016227:Benzoquinones; D011619:Psychotropic Drugs; D011743:Pyrimidines; D011759:Pyrrolidines; D011760:Pyrrolidinones; C064122:BMY 21502; D014451:Ubiquinone; D012601:Scopolamine; C036619:idebenone; D011190:Potassium Cyanide; C040619:oxiracetam