Mergrocriptine

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)

The authors have examined the protective effects of CBM 36-733 (2-methyl-alpha-ergocryptine) on experimental cerebral ischaemia in spontaneously hypertensive rats (SHR). SHR aged 6 months were divided into four groups; a vehicle-treated group, and CBM 36-733 0.01, 0.1 or 1.0 mg/kg i.v. treated groups. After anaesthesia, the bilateral common carotid artery was ligated (BCL) and supratentorial cerebral ischaemia was produced for 1 h. Cerebral blood flow to the parietal cortex was repeatedly measured by the H2 clearance technique. Brain tissue lactate, adenosine triphosphate (ATP) and pyruvate were determined by enzymatic methods. By BCL, cerebral cortical blood flow decreased to 9-19% of the resting value at 30 min and further to 5-11% at 60 min. Blood flow reduction was not altered by CBM 36-733 administration. At 1 h ischaemia, brain tissue lactate greatly increased to 27.5 +/- 2.6 (mean +/- SEM) mmol/kg in the vehicle-treated SHR, while it showed less increase, to 7.5 +/- 1.4, in the CBM 36-733 0.1 mg/kg group. Brain ATP decreased to 1.31 +/- 0.05 in vehicle-treated SHR after 1 h BCL, but it changed little, retaining almost normal levels (2.60 +/- 0.19) in rats treated with 0.1 mg/kg CBM 36-733, followed by 1.0 and 0.01 mg/kg, suggesting a beneficial effect of CBM 36-733 on the ischaemic cerebral metabolism. The present results suggest that CBM 36-733 has a protective effect on the brain against ischaemia by improving cerebral metabolism while not affecting haemodynamics.