The effects of
mergocriptine (2-methyl-a-
ergocryptine; CBM36-733; CAS 81968-16-3) on
ischemia-induced brain damages were studied using both a global and a focal
ischemia model. First, immediately after 5 min of forebrain
ischemia induced by
ligation of the bilateral carotid arteries of Mongolian gerbils, the animals were intraperitoneally injected with 3 mg/kg or 10 mg/kg
CBM36-733. Seven days after
ischemia, perfusion-fixed brains were processed by conventional histology. The number of neurons per mm in the CA 1 pyramidal cell layer was calculated and they were labelled neuronal density. In the control group, the neuronal density was 69.7 +/- 7.2 (mean +/- SEM/mm), in the vehicle group and 3 mg/kg of
CBM36-733 treated group, they were 12.2 +/- 4.4 and 11.6 +/- 5.1, respectively. The neuronal density in the 10 mg/kg of
CBM36-733 treated group was 42.2 +/- 8.4. These data indicate that 10 mg/kg of
CBM36-733 protects on the CA 1 neurons against
ischemia induced delayed neuronal death. Second, the effect of long-term administration of 3 mg/kg
CBM36-733 on focal
brain ischemia of the rats was studied by measuring regional cerebral blood flow and
glucose metabolism by autoradiograms. After 90 min of
middle cerebral artery occlusion, the rats were intraperitoneally injected with 3 mg/kg of
CBM36-733 every day for 2 weeks. There were no significant differences in cerebral blood flow and
glucose metabolism between the treated group and the vehicle group.(ABSTRACT TRUNCATED AT 250 WORDS)