ergoline and Brain-Ischemia

Acute cerebral ischaemia may take considerable advantages of an adequate intensive therapy associated with a specific treatment of cerebral oedemas, especially in terms of mortality-rate reduction. Moreover, target treatment of acute cerebral ischaemia may produce excellent results in severe cases selected by means of EEG-chronospectrography. Double-blind, randomized comparison between nicergolin and buflomedil especialls showed that the latter reduces mortality three times as much as nicergolin, and leads to a 200% increment in the complete recovery of the "functio laesa", limited to those cases, which showed an appreciable improvement following EEG-chronospectrographical survey.

Topics: Acute Disease; Aged; Brain Ischemia; Cerebrovascular Circulation; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Electroencephalography; Ergolines; Female; Humans; Male; Middle Aged; Nicergoline; Pyrrolidines; Random Allocation

The activity of (-)eburnamonine, a substance acting on the cerebral circulation and metabolism, was compared with that of nicergoline in a double-blind study carried out on a group of 28 patients (16 males and 12 females), suffering from established chronic brain ischemia. The treatment consisted of the administration for the first 5 days of 80 mg/day and for the following days of 60 mg/day of (-)eburnamonine, in 14 subjects. Nicergoline was administered to the other 14 subjects: 20 mg/day for the first 5 days and then 15 mg/day. The treatment was protracted for at least 20 days. (-)Eburnamonine appeared to influence some symptoms more rapidly and significantly than nicergoline. After 20 days of treatment the overall improvement obtained with (-)eburnamonine was 31 and 18% with nicergoline. No side effects or impairment of the biochemical tests appeared during either treatment.

Topics: Aged; Brain; Brain Ischemia; Cerebrovascular Circulation; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Ergolines; Female; Humans; Male; Nicergoline; Placebos; Vasodilator Agents; Vinca Alkaloids

It has been suggested that ergoline dopamine agonists can cause ischemic complications. The effect of dopamine agonists in general on the prevalence of ischemic events in patients with Parkinson's disease (PD) has not been studied.. Our aim was to investigate the association between the use of dopamine agonists and hospitalization due to ischemic events in patients with PD.. We performed a nested case-control study using the PHARMO Institute for Drug Outcome Research database. All patients issued at least one prescription for levodopa after the age of 55 years between 1994 and 2006 were initially identified. Cases were patients who were hospitalized for the first time after November 1997 for an ischemic event and were matched to as many as four controls. Exposure to dopamine agonists during the year preceding the index date was identified.. The study population consisted of 542 cases and 2,155 controls. The mean effect of dopamine agonist use 1 year prior to the index date on ischemic events requiring hospitalization is shown with 95% probability in the 0.95-1.49 range. Stratified results according to the type of dopamine agonist showed no risk differences between ergoline and nonergoline agonists.. This study does not support an association between dopamine agonist use and an increased risk of ischemic events requiring hospitalization.

Topics: Aged; Aged, 80 and over; Antiparkinson Agents; Brain Ischemia; Case-Control Studies; Databases, Factual; Dopamine Agonists; Drug Prescriptions; Ergolines; Female; Hospitalization; Humans; Ischemia; Levodopa; Male; Myocardial Ischemia; Netherlands; Parkinson Disease; Practice Patterns, Physicians'; Prevalence; Raynaud Disease; Severity of Illness Index

Topics: Brain Ischemia; Cabergoline; Dopamine Agonists; Dose-Response Relationship, Drug; Ergolines; Fatal Outcome; Fibrosis; Heart Valve Prosthesis Implantation; Humans; Intestinal Obstruction; Male; Middle Aged; Mitral Valve Insufficiency; Pituitary Neoplasms; Prolactinoma; Tricuspid Valve Insufficiency; Ventricular Dysfunction, Left

The effect of dopamine (DA) receptor agonists and antagonists on hypoxia/hypoglycemia (ischemia)-induced decrease in CA1 presynaptic fiber spikes elicited by the stimulation of Schaffer collateral were investigated using hippocampal slices. Treatment with D1 dopamine receptor antagonist, SCH23390 produced a concentration-dependent attenuation of the ischemia-induced decrease of presynaptic potentials. The magnitude of recovery of the CA1 presynaptic potential in SCH233390-treated slices at 10 and 100 microM was 28 and 54%, respectively. Whereas, treatment with D1 dopamine receptor agonist, SKF38393 exacerbated the ischemia-induced decrease in the CA1 presynaptic potential. The decrease of CA1 presynaptic potential by ischemia was affected by neither D2 dopamine receptor agonist, bromocriptin and quinpirole nor D2 dopamine receptor antagonist, sulpiride. The neuroprotective effect of SCH23390 was completely blocked by cotreatment with SKF38393. The present results demonstrated that the blockade of D1 dopamine receptor function played a neuroprotective role in ischemic damage, suggesting a facilitatory role of D1 dopamine receptor-operated function in ischemia-induced neuronal deficits.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Action Potentials; Analysis of Variance; Animals; Benzazepines; Brain Ischemia; Bromocriptine; Dopamine Agonists; Ergolines; Hippocampus; In Vitro Techniques; Male; Nerve Fibers; Presynaptic Terminals; Quinpirole; Rats; Rats, Wistar; Receptors, Dopamine D1; Sulpiride

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

Topics: Adult; Brain; Brain Ischemia; Drug Evaluation; Ergolines; Humans; Injections, Intravenous; Intracranial Arteriosclerosis; Middle Aged; Nicergoline; Plethysmography, Impedance; Tablets; Time Factors

The cerebroprotective effect of nicergoline was studied using the following experimental methods: hypobaric and anoxic hypoxia in mice, complete ischemia by decapitation in mice, incomplete ischemia by bilateral carotid ligation in rats, hemic hypoxia in rats and asphyxic anoxia in cats. Xanthinol nicotinate, vincamine, vinpocetine and cinnarizine were used as reference drugs. In hypobaric hypoxia and complete ischemia by decapitation the interaction of nicergoline with the effect of prostacyclin (PGI2) was investigated. Nicergoline showed cerebroprotective effect of varying potency in all the methods used except asphyxic anoxia. Nicergoline manifested a synergic effect with PGI2 shifting its anti-hypoxic dose-response curve to the left.

Topics: Animals; Brain Ischemia; Cats; Cerebrovascular Circulation; Drug Interactions; Epoprostenol; Ergolines; Female; Hypoxia; Male; Mice; Nicergoline; Rats; Rats, Inbred Strains

Topics: Animals; Brain Ischemia; Cerebrovascular Circulation; Dogs; Ergolines; Male; Nicergoline; Oxygen Consumption; Resuscitation; Time Factors

Effects of nicergoline on ischemic brain damages induced by bilateral carotid arterial ligation (BCAL) in ICR-strain mice and mongolian gerbils and lipid peroxide formation (LPOF) in normal brain homogenate of rats were compared with those of dihydroergotoxine (DHE). In mice, nicergoline (16 mg/kg, i.p.) significantly reduced the cumulative mortality rate after BCAL (from 80-83% in the control to 50-55%). In gerbils, nicergoline (32 mg/kg, i.p.) significantly prolonged the mean onset time of ischemic seizure following recirculation after the 30-min BCAL (from 45.8 min in the control to 94.9 min). DHE also showed protective effects in these animals. In the ischemic brain of mice, marked decreases of creatine-P, ATP, glucose and glycogen; a remarkable increase of lactate; and elevation of L/P ratio were observed 1 to 10 min after BCAL. Nicergoline (16 mg/kg, i.p.) slightly prevented these decreases and significantly suppressed the increase of lactate and the elevation of L/P ratio 2 min after BCAL. The inhibitory action of nicergoline (20-100 microM) on LPOF is more potent than those of alpha-tocopherol and DHE. These results suggest that nicergoline may have protective effects against ischemic brain damages due to its ameliorating action on cerebral energy metabolism and partially due to its inhibitory action of LPOF.

Topics: Animals; Brain; Brain Ischemia; Dihydroergotamine; Energy Metabolism; Ergolines; Female; Gerbillinae; Lipid Peroxides; Male; Mice; Mice, Inbred ICR; Nicergoline; Rats; Rats, Inbred Strains; Seizures

The effects of a new eburnamenine derivative (3 beta,14 alpha, 16 alpha)-(+/-)-14,15-dihydro-20,21-dinoreburnamenin-14-ol (vindeburnol, RU 24722) on EEG, on brain energy metabolism and on local cerebral blood flow (LCBF) and in different experimental models of cerebral insufficiency were compared with those of vincamine, vinburnine (1-eburnamonine), dihydroergotoxine mesilate and nicergoline. Vindeburnol at 2 mg/kg i.v., increased the EEG resistance time in rats subjected to asphyxia anoxia and at 10 mg/kg s.c., significantly improved the electrocortical recovery of gerbils subjected to a 10-min cerebral ischemia. Vindeburnol (10 mg/kg i.p.) significantly retarded glucose, phosphocreatine and adenosine triphosphate utilization and lactate production in mouse brain during 10 s of decapitation ischemia. The cerebral metabolic rate was 10.34 mmol/kg/min, which was about 50% of the control value. At 10 mg/kg i.p., the product induced a slight and transient increase in LCBF. Vincamine improved the early phase of the postischemic electrocortical recovery in the gerbil, had no effect on cerebral energy substrates and slightly increased the LCBF for 15 min. Dihydroergotoxine mesilate improved the early phase of the electrocortical recovery in gerbils subjected to ischemia, did not significantly modify the energy substrates and rapidly increased the LCBF, which was normal after 30 min. Vinburnine and nicergoline were inactive in the cerebral insufficiency models used and did not significantly modify cerebral energy metabolism. These results show that vindeburnol has a different pharmacological profile from vincamine, vinburnine, dihydroergotoxine mesilate and nicergoline, and suggest that vindeburnol may be therapeutically effective in cerebral insufficiency.

Topics: Animals; Brain Ischemia; Cerebral Cortex; Cerebrovascular Circulation; Cerebrovascular Disorders; Dihydroergotoxine; Electroencephalography; Ergolines; Gerbillinae; Male; Mice; Mice, Inbred Strains; Nicergoline; Rats; Rats, Inbred Strains; Vinca Alkaloids; Vincamine

The effect of the alpha-adrenoblockers, nicergoline (N) and dihydroergotoxin (DHET), on the cerebral vessels and the systemic hemodynamics was studied in 152 patients with acute and chronic vascular diseases of the brain. It was established that the hypotensive action of alpha-blockers was the greater the higher was the initial arterial hypertension. REG conducted during an hour after the intravenous administration of N and DHET revealed an increase in the pulse blood filling and an improvement of the arterial tone. Changes in vascular resistance were heterogeneous. Both drugs induced the venous outflow but there were no signs of venous hypotension. An improvement in the systemic and cerebral hemodynamics correlated with clinical improvement.

Topics: Blood Pressure; Brain Ischemia; Cerebrovascular Circulation; Cerebrovascular Disorders; Dihydroergotoxine; Ergolines; Humans; Nicergoline; Plethysmography, Impedance; Subarachnoid Hemorrhage; Vascular Resistance

Unilateral cerebral ischaemia was induced in 18-month-old Long-Evans rats by injection of 2,000 labelled microspheres (phi 50 microns) into the carotid blood stream. This results in an ipsilateral decrease in cerebral blood flow, development of severe oedema and modifications of glucose uptake and consumption. Furthermore, this ischaemia led to a deterioration of the avoidance response in conditioned animals. All these disturbances, including the cerebral oedema, diminished with nicergoline pretreatment.

Topics: Aging; Animals; Avoidance Learning; Behavior, Animal; Brain; Brain Ischemia; Cerebrovascular Circulation; Deoxyglucose; Disease Models, Animal; Ergolines; Hemodynamics; Male; Nicergoline; Rats; Rats, Inbred Strains

Topics: Animals; Blood Pressure; Brain Ischemia; Cats; Cerebrovascular Circulation; Electroencephalography; Ergolines; Homeostasis; Hypertension; Hypotension; Nifedipine; Papaverine; Vasodilation

Topics: Aged; Blood Pressure; Brain Ischemia; Cardiac Output; Cerebrovascular Circulation; Chronic Disease; Electroencephalography; Ergolines; Female; Heart Rate; Humans; Male; Middle Aged; Nicergoline

Topics: Adult; Aged; Brain Ischemia; Drug Tolerance; Ergolines; Female; Humans; Male; Middle Aged; Nicergoline