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 [bifemelane hydrochloride] 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 the animals (6-40 wk old), the mean survival time of the immature group (6-7 wk) was long (3.6 h), but variable. That of the 10-40 wk group was relatively stable (1.9-2.4 h), but that of the older group (30-40 wk) tended to be reduced. The effects of drugs on this model were studied in 10-15 wk old male Mongolian gerbils. The mean survival time in the control groups was 2.3-2.4 h. After a single administration of MCI-2016 at doses of 25 mg/kg, i.p., and 100 mg/kg, p.o. [per os] the mean survival time were 8.1 and 6.4 h, respectively. In these cases, some animals survived over 12 h, while no animals surviving > 12 h were observed in the control group. In this model, animals showed severe neurological symptoms. This 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.