Protective effects of 4 o benzylphenoxy n methylbutylamine hydrochloride bifemelane on acutely induced cerebral ischemia in mongolian gerbils and spontaneously hypertensive rats
Fujishima, M.; Ishitsuka, T.; Omae, T.
Brain and Nerve 36(10): 999-1004
1984
Accession: 006210239
Effects of new antihypoxic agent (bifemelane) on survival and brain metabolism were studied in acute cerebral ischemia induced by bilateral carotid artery ligation in Mongolian gerbils and SHR [spontaneously hypertensive rats]. Either 10 mg/kg or 30 mg/kg body wt of bifemelane dissolved in distilled water was i.p. administered 1 h in gerbils and 1.5 h in SHR prior to carotid ligation and the same amount of vehicle was also given in similar manner to control animals. Brain tissue metabolites such as lactate, pyruvate and ATP were determined by using the enzymatic technique in the ischemic brain frozen in situ 1 h after carotid ligations in SHR. Mean survival times following carotid ligations were 186 .+-. 255 min (.+-. SD) in control gerbils, 429 .+-. 455 min in those with 10 mg/kg of bifemelane, and 310 .+-. 429 min in those with 30 mg/kg, respectively, its difference between control and 10 mg/kg group being significant (P < 0.05). Supratentorial lactate concentrations in the ischemic brains of SHR were substantially the same among the groups, whereas ATP levels were 0.62 .+-. 0.24 mM/kg in control animals, 1.10 .+-. 0.67 mM/kg in rats with 10 mg/kg of the drug, and 1.13 .+-. 0.42 mM/kg in those with 30m g/kg, respectively. In animals with a high dose pretreatment, the reduction of ATP was significantly smaller than that in control (P < 0.02), indicating that this agent prevents a decline of high energy phosphate in the ischemic brain although anaerobic metabolites increase similarly in animals of all experiment groups. Bifemelane may have antiischemic efect on acutely-induced cerebral ischema and its effect is likely due to metabolism-stimulating rather than vasodilating action.