ergoline and mergocriptine

Mergocriptine (CBM 36-733, CAS 81968-16-3) is an ergot alkaloid derivative and a dopaminergic agonist. Effects of mergocriptine on cerebral circulation and metabolism were examined by monitoring cerebral tissue oxygen and carbon dioxide tension (BrPO2, BrPCO2), cerebral blood flow (CBF) and blood pressure (BP) in 10 cats. Mergocriptine (10 micrograms/kg) infused into the carotid artery produced a significant increase in CBF during the administration followed by a decrease in BrPO2 in parallel with a significant decrease in BP.

Topics: Animals; Blood Pressure; Brain Chemistry; Carbon Dioxide; Cats; Cerebrovascular Circulation; Ergolines; Oxygen Consumption

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)

Topics: Animals; Autoradiography; Brain; Brain Chemistry; Brain Ischemia; Cell Death; Ergolines; Gerbillinae; Male; Neurons; Pyramidal Tracts; Rats; Rats, Inbred Strains

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.

Topics: Adenosine Triphosphate; Animals; Brain; Brain Ischemia; Ergolines; Female; Hemodynamics; Lactates; Lactic Acid; Pyruvates; Pyruvic Acid; Rats; Rats, Inbred SHR

The effect of mergocryptine, a new ergot alkaloid, on the cerebral dopaminergic systems was examined using Wistar rats. The administration of mergocryptine (1 and 10 mg/kg i.p.) induced a significant suppression of striatal dopamine (DA) turnover. In vitro addition of mergocryptine (0.01-100 microM) induced a dose-dependent suppression of the release of [3H]DA from striatal slices. Mergocryptine inhibited [3H]apomorphine binding to a striatal synaptosomal fraction, and its IC50 value was found to be 0.23 microM. Pretreatment with apomorphine (100 micrograms/kg s.c.) showed an additive effect on the mergocryptine (10 mg/kg)-induced suppression of DA turnover. These results suggest that mergocryptine may induce the suppression of striatal DA turnover by reducing DA release via the stimulation of presynaptic dopaminergic autoreceptors.

Topics: Animals; Apomorphine; Benzazepines; Corpus Striatum; Dopamine; Ergolines; Half-Life; Male; Quinuclidinyl Benzilate; Rats; Rats, Inbred Strains; Receptors, Dopamine; Spiperone

Effects of repeated administration of mergocriptine (CBM36-733: CBM), a long-acting ergot derivative with an agonistic action on both dopamine D1 and D2 receptors, as well as interaction between CBM and methamphetamine (MAP: 2 mg/kg, s.c.), were investigated by ambulatory activity in mice. CBM at 4 mg/kg significantly suppressed the ambulatory activity, but significantly increased it at 16 mg/kg in the drug-naive mice. However, 4 and 8 mg/kg of CBM were effective for increasing the ambulatory activity when these doses were repeatedly administered for 9 times at intervals of 7 days. The same treatment with 16 mg/kg of CBM produced a reverse tolerance to the ambulation-increasing effect. The mice that had received CBM at 1 and 2 mg/kg, but not 4-16 mg/kg, demonstrated a significantly lower sensitivity to MAP than the saline-experienced mice. On the other hand, the repeated MAP administration induced not only a reverse tolerance to itself, but also a cross reverse tolerance to 8 and 16 mg/kg of CBM. Furthermore, the established reverse tolerance to MAP was scarcely attenuated by the repeated treatment with any doses of CBM, but rather enhanced by 8 and 16 mg/kg of CBM. The present results indicate that, although the dose-effect relations are partially different, the behavioral characteristics of CBM were almost identical with those of bromocriptine, another long-acting ergot derivative having antagonistic and agonistic actions on dopamine D1 and D2 receptors, respectively.

Topics: Animals; Behavior, Animal; Delayed-Action Preparations; Drug Interactions; Ergolines; Methamphetamine; Mice; Motor Activity; Time Factors