Effect of MCI-2016 (bifemelane hydrochloride) on cerebral ischemia following ligation of both common carotid arteries in Mongolian gerbils

Abstract

Cerebral protective effect of MCI-2016 and influence of age on survival time in the cerebral ischemic model induced by bilateral-carotid-arterial ligation in male Mongolian gerbils were studied. Of all animals (6 to 40 weeks old), the mean survival time of the immature group (6 to 7 weeks) was long (3.6 hr), but variable, and that of the 10 to 40 weeks group was relatively stable (1.9 ?? 2.4 hr), but that of the older group (30 ?? 40 weeks) inclined to be reduced. Effects of drugs on this model were studied in 10 to 15 weeks old male Mongolian gerbils. The mean survival time in the control groups was 2.3 ?? 2.4 hr. After a single administration of MCI-2016 at doses of 25 mg/kg, i.p., and 100 mg/kg, p.o., the mean survival time were 8.1 and 6.4 hr, respectively. In these cases, some animals survived over 12 hr, while no animals surviving over 12 hr were observed in the control group. In this model, animals showed severe neurological symptoms. This, however, tended to be depressed by the administration of MCI-2016 at a dose of 25 mg/kg, i.p., which was observed early after ligation. A cerebral metabolic activator, Ca-hopantenate, slightly increased the survival time at a dose of 100 mg/kg, i.p., and a cerebral vasodilator, ifenprodil, was not effective. Subsequently, consecutive administration of MCI-2016 at a dose of 25 and 50 mg/kg, p.o., was more effective than a single administration of MCI-2016 at each dose. The mechanism for the cerebral protective effect of MCI-2016 was discussed.