ergoline and Ischemia

10-Methoxy-1,6-dimethyl-ergoline-8 beta-methanol-(5-bromonicotinate) (nicergoline, Sermion) shows a strong alpha-blocking activity both in vitro and in vivo. Various studies (dog, cat, rabbit, rat, mouse, guinea-pig) show that nicergoline affects only slightly blood pressure and heart rate and increases the blood flow in brain and hind limb without affecting the splanchnic and aortic flow in normal animals. Nicergoline does not interfere with CNS functions unless applied in high doses. It stimulates the muscle oxidative metabolism and function and lacks any emetic and hallucinogenic activity. Its acute and chronic toxicity in different animal species is very low.

Topics: Adrenergic alpha-Antagonists; Animals; Cats; Central Nervous System; Cholesterol; Ergolines; Guinea Pigs; Hemodynamics; Hypoxia; Ischemia; Muscles; Nicergoline; Platelet Aggregation; Rabbits; Rats

Ischemia and the metabolic disorder it entails would seem to be the pathogenic mechanism behind acute cochlear deafness, irrespective of the triggering process. The prognosis is entirely dependent on the rapid initiation of an effective treatment. At the end of a double-blind therapeutic trial comparing Ginkgo biloba extract and a standard alpha blocker (nicergoline), a significant recovery was observed in both therapeutic groups, but improvement was distinctly better in the Ginkgo biloba group.

Topics: Audiometry, Pure-Tone; Audiometry, Speech; Clinical Trials as Topic; Cochlea; Ergolines; Hearing Loss; Hearing Loss, Conductive; Humans; Ischemia; Middle Aged; Nicergoline; Plant Extracts; Plants, Medicinal; Random Allocation; Trees

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: Antiparkinson Agents; Brain Stem Infarctions; Cabergoline; Dose-Response Relationship, Drug; Ergolines; Humans; Ischemia; Male; Middle Aged; Tremor

Dopamine receptor agonists are protective in different models of neurodegeneration by both receptor-dependent and -independent mechanisms. We used SH-SY5Y cells, differentiated into neuron-like type, to evaluate if cabergoline, a dopamine D2 receptor agonist endowed with anti-oxidant activity, protects the cells against ischemia (oxygen-glucose deprivation model). Cabergoline protected the cells from ischemia-induced cell death in a concentration-dependent manner (EC(50)=1.2 microM), as demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release, and fluorescein diacetate-propidium iodide staining. This effect, observed even when the drug was added after oxygen-glucose deprivation, was not mediated by either dopamine D2 receptor activation or anti-apoptotic Bcl-2 protein over-expression (Western blotting analysis), but was linked to a reduction in cellular free radical loading (2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining) and membrane lipid peroxidation (thiobarbituric acid-reacting test). In conclusion, cabergoline protects in vitro neurons against ischemia-induced cell death, suggesting its possible use in the therapy of other neurodegenerative diseases in addition to Parkinson's disease.

Topics: Animals; Antioxidants; Cabergoline; Cell Death; Cell Hypoxia; Cell Line, Transformed; Cell Line, Tumor; Cell Survival; Disease Models, Animal; Dopamine Agonists; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Ergolines; Free Radical Scavengers; Free Radicals; Gene Expression; Genes, bcl-2; Glucose; Haloperidol; Humans; Ischemia; Neurons; Thiobarbituric Acid Reactive Substances; Time Factors; Tretinoin; Vitamin E

Ischemic necrosis resulting from vasospasm is a common complication in skin flap surgery, and serotonin released by traumatized platelets is likely to play an important role in the pathogenesis of skin vasospasm in flap surgery. We studied the pathogenic role of serotonin and its pharmacologic intervention thereof in skin flap ischemic necrosis in pigs. We observed that serotonin caused a concentration-dependent (10(-8)-10(-5) M) increase in perfusion pressure in isolated perfused pig skin flaps. This vasoconstrictive effect of serotonin was blocked by S1C/2-serotonergic receptor antagonists LY53857 (10(-5) M) and ketanserin (10(-5) M), but not by an alpha 1-adrenoceptor antagonist (prazosin 10(-5) M), or a thromboxane A2 (TxA2)/endoperoxide receptor antagonist (SQ30741 10(-5) M). The vasoconstrictive effect of serotonin was more pronounced (p < 0.05) in the presence of an endothelium-derived nitric oxide (NO) synthesis inhibitor [N omega-monomethyl-L-arginine (L-NA) or NG-nitro-L-arginine (L-NMMA) 10(-5) M] but not a cyclooxygenase inhibitor (indomethacin 10(-5) M). In in vivo studies, serotonin infusion (5 micrograms/kg/min intravenously, i.v.) significantly (p < 0.05) decreased pig random pattern skin flap capillary blood flow. This in vivo vascular effect was also completely blocked in pigs pretreated with LY53857 (0.4 mg/kg i.v.). In a separate experiment without serotonin infusion, i.v. prazosin (2-8 micrograms/kg), dazmegrel (2-6 mg/kg), or SQ30741 (2-4 mg/kg) had no significant effect on skin flap capillary blood flow as compared with control. On the other hand, i.v. sergolexole or LY53857 significantly (p < 0.05) increased skin flap capillary blood flow in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenergic alpha-Antagonists; Animals; Arginine; Dose-Response Relationship, Drug; Ergolines; In Vitro Techniques; Ischemia; Ketanserin; Necrosis; omega-N-Methylarginine; Prostaglandin H2; Prostaglandins H; Regional Blood Flow; Serotonin; Serotonin Antagonists; Skin; Surgical Flaps; Swine; Thromboxane A2; Vasoconstriction

Three experiments were conducted to study the effect of ketanserin and LY53857, S2-serotonergic receptor antagonists, on skin blood flow and viability in acute random pattern skin flaps (4 x 10 cm) in the pig. In experiment 1, the dose-response effect of intravenous ketanserin (0, 0.15, 0.25, 0.35, and 0.50 mg/kg) on skin flap capillary blood flow was studied 6 hr after skin flap surgery, using the radioactive microsphere (15 microns) technique and under pentobarbital anesthesia. Significant (P less than 0.05) increase in skin flap blood flow was seen at the dosages of 0.25 and 0.35 mg/kg compared with the saline-treated control. In experiment 2, the effect of five-day intramuscular ketanserin and LY53857 treatment (0.30 mg/kg/day; in divided doses) on skin flap viability was studied. The drug treatments were started two days preoperatively. It was observed that the length of skin flap viability in ketanserin (6.6 +/- 0.2 cm; n = 40 flaps) and LY53857 (6.8 +/- 0.3 cm; n = 40 flaps) treated flaps were significantly (P less than 0.05) higher than the saline-treated control (5.5 +/- 0.1 cm; n = 48 flaps). Ketanserin treatment started 30 min after flap surgery also significantly (P less than 0.05) increased the length of skin flap viability (6.1 +/- 0.1 cm) compared with the control. There was no significant difference in skin viability between ketanserin and LY53857 treated skin flaps. The preceding study on the effect of ketanserin treatment on random pattern skin flap viability was repeated in experiment 3. Again, it was observed that intramuscular ketanserin treatment significantly (P less than 0.05) increased the skin flap viability. It was concluded that ketanserin and LY53857 treatment resulted in significant augmentation of porcine acute random pattern skin flap viability. This is the first experimental evidence to indicate that S2-serotonergic receptors participate in the pathogenesis of skin flap ischemia.

Topics: Animals; Dose-Response Relationship, Drug; Ergolines; Graft Survival; Ischemia; Ketanserin; Regional Blood Flow; Serotonin Antagonists; Skin; Surgical Flaps; Swine

Clinical ergotism as seen today results almost exclusively from the excessive intake of ergotamine tartrate in the treatment of migraine headache. Although both gangrenous and convulsive symptoms are seen in naturally occurring ergotism resulting from the ingestion of fungus infected rye, only gangrenous ergotism has been reported following the excessive ingestion of ergotamine tartrate. The symptoms of both iatrogenic and naturally occurring ergotism appear to result from regional ischemia caused by ergot induced vasospasm. This report discribes experiences in the diagnosis and management of two patients with unusual manifestations of iatrogenic ergotism. One patient presented with ischemia of all extremities and bilateral foot drop probably due to ischemic damage to the common peroneal nerves, a finding not previously described in ergot intoxication. The foot drop totally resolved in several months following the discontinuation of ergot. A second patient presented with unilateral leg ischemia and transient monocular blindness, both of which resolved after discontinuation of ergot. Both patients displayed typical angiographic findings of ergotism. There is no convincing evidence that any treatment other than discontinuation of ergotamine is of benefit in the treatment of iatrogenic ergotism.

Topics: Adult; Angiography; Arm; Blindness; Ergolines; Ergotamines; Ergotism; Extremities; Female; Femoral Artery; Humans; Ischemia; Leg; Male; Middle Aged; Peripheral Nervous System Diseases; Peroneal Nerve; Popliteal Artery; Retinal Vessels

Topics: Angiography; Angiotensin II; Animals; Dogs; Ergolines; Ergonovine; Female; Graft Rejection; Hemodynamics; Ischemia; Kidney; Kidney Transplantation; Models, Biological; Norepinephrine; Phenoxybenzamine; Propranolol; Tolazoline; Transplantation Immunology; Transplantation, Autologous; Vasoconstrictor Agents; Vasopressins