[Protective effects of 4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride (bifemelane) on acutely induced cerebral ischemia in Mongolian gerbils and spontaneously hypertensive rats (SHR)].
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. Either 10 mg/kg or 30 mg/kg body weight of bifemelane solved in distilled water was intraperitoneally administered 1 hr in gerbils and 1.5 hrs in SHR prior to carotid ligation, and same amount of vehicle was also given in similar manner for 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 hr 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 less than 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 30 mg/kg, respectively. In animals with a high dose pretreatment, the reduction of ATP was significantly smaller than that in control (P less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D004195:Disease Models, Animal; D005260:Female; D005849:Gerbillinae; D005947:Glucose / Q000378:metabolism; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D013997:Time Factors
D001559:Benzhydryl Compounds; D005947:Glucose; C031906:bifemelane