ergoline and Hypoxia

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

The effects of 10-methoxy-1,6-dimethyl-ergoline-8 beta-methanol(5-bromonicotinate) (nicergoline, Sermion) on the energy metabolism in the animal CNS during and after cerebral hypoxia and ischemia have been studied by various authors by different methodological approaches. For this purpose both electrophysiological (EEG and cortically evoked potentials) and neurochemical parameters (adenylates, creatinphosphate and some intermediates of glycolysis and Krebs cycle) were analysed in dogs and cats. These studies concordantly show that nicergoline exerts a favourable activity during the post-hypoxic and post-ischemic period. In fact the recovery of the electrophysiological and neurochemical parameters is always more rapid in nicergoline-treated animals than in controls. The effects of nicergoline on the EEG pattern, on the energy potential and citrate concentration are particularly interesting.

Topics: Animals; Brain; Brain Chemistry; Dogs; Ergolines; Hypoxia; Kidney; Nicergoline

The anatomical factors involved in upper airway closure of obstructive sleep apnea (OSA) have been established. However, the mechanisms of repetitive OSA are not well understood. We found that dorsomedial medullary 5-HT2 receptor activity is compensated for by hypercapnia and elicits the immediate onset of poikilocapnic hypoxic ventilatory airway responses. Therefore, the aim of this study was to test the hypothesis that hypercapnia compensates for the immediate onset of poikilocapnic hypoxic ventilatory airway responses induced by dorsomedial medullary 5-HT2 receptors. Adult male mice (C57BL/6N) were intraperitoneally anesthetized with pentobarbital sodium. Microdialysis probes were inserted into the dorsomedial medulla oblongata of the mice. The mice were placed in a double-chamber plethysmograph and were allowed to acclimatize and recover from anesthesia. Mice were then exposed to hypercapnic hypoxic gases (7 % O2/5 % CO2 in N2) with or without 5-HT2-antagonist (10(-5) M LY-53857) perfusion. Respiratory curves through the head and body chambers were recorded to measure ventilatory airway variables. Extracellular fluid was collected every 5 min for HPLC analysis of 5-HT concentration. Hypercapnic hypoxia elicited neither delayed onset of ventilatory augmentation nor immediate airway narrowing with dorsomedial medullary 5-HT2 antagonism. Hypoxic polypnea was shifted downward. The increases in dorsomedial medullary 5-HT release and ventilatory volume were not affected with or without 5-HT2 activity. In conclusion, the onset of poikilocapnic hypoxic ventilatory airway responses mediated via dorsomedial medullary 5-HT2 activity is compensated for by hypercapnia. Maintenance of PCO2 level and CO2 responsiveness, especially with lowered 5-HT2 activity, may be important for preventing repetitive OSA.

Topics: Animals; Disease Models, Animal; Ergolines; Hypercapnia; Hypoxia; Male; Medulla Oblongata; Mice; Mice, Inbred C57BL; Receptors, Serotonin, 5-HT2; Serotonin; Serotonin Antagonists

The dorsomedial medulla oblongata (DMM) includes the solitary tract nucleus and the hypoglossal nucleus, to which 5-HT neurons project. Effects of 5-HT in the DMM on ventilatory augmentation and airway dilation are mediated via 5-HT2 receptors, which interact with the CO(2) drive. The interaction may elicit cycles between hyperventilation with airway dilation and hypoventilation with airway narrowing. In the present study, effects of 5-HT2 receptors in the DMM on hypoxic ventilatory and airway responses were investigated, while 5-HT release in the DMM was monitored. Adult male mice were anesthetized, and then a microdialysis probe was inserted into the DMM. The mice were placed in a double-chamber plethysmograph. After recovery from anesthesia, the mice were exposed to hypoxic gas (7% O(2) in N(2)) for 5 min with or without a 5-HT2 receptor antagonist (LY-53857) perfused in the DMM. 5-HT release in the DMM was increased by hypoxia regardless of the presence of LY-53857. Immediate onset and the peak of initial hypoxic hyperventilatory responses were delayed. Subsequent ventilatory decline and airway dilation during initial hypoxic hyperventilation were suppressed with LY-53857. These results suggest that 5-HT release increased by hypoxia acts on 5-HT2 receptors in the DMM, which contributes to the immediate onset of initial hypoxic hyperventilation, airway dilation, and subsequent ventilatory decline. Hypoxic ventilatory and airway responses mediated via 5-HT2 receptors in the DMM may play roles in immediate rescue and defensive adaptation for hypoxia and may be included in periodic breathing and the pathogenesis of obstructive sleep apnea.

Topics: Airway Resistance; Animals; Body Weight; Disease Models, Animal; Ergolines; Hyperventilation; Hypoxia; Lung; Male; Medulla Oblongata; Mice; Mice, Inbred C57BL; Microdialysis; Plethysmography; Pulmonary Ventilation; Receptors, Serotonin, 5-HT2; Respiratory Mechanics; Serotonin; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Sleep Apnea, Obstructive; Time Factors

To study specific serotonin (5-hydroxytryptamine [5-HT]) receptor subtype antagonists in an animal model of posthypoxic myoclonus.. Although serotonergic system dysfunction is implicated in posthypoxic myoclonus, anatomic specificity and linkage to receptor subtypes are not delineated.. The authors performed a pharmacologic study to identify specific serotonin receptor subtype antagonists effective in inhibiting myoclonus in posthypoxic rats. Sprague-Dawley rats underwent cardiac arrest for 8 minutes and were resuscitated. On the day of pharmacologic testing, animals were rated every 10 minutes at -30 minutes to time 0 (drug injection) and from +60 to +150 minutes. Using a blinded methodology, animals were injected with normal saline, vehicle, or one of seven serotonin antagonists given at a dose that maintains serotonin receptor subtype specificity: WAY100135 (5-HT1A), methiothepin mesylate (5-HT1B/1D/2), mesulergine hydrochloride (5-HT2A/2B), GR 127935 (5-HT1D), SR 46349 (5-HT2), ondansetron (5-HT3), or GR 125487 (5-HT4). Drugs that produced a significant decrease in myoclonus compared with the control were studied in a dose-response study with six doses across a range from the original dose studied to 10% of that dose.. Two drugs were significantly different from placebo: methiothepin mesylate and mesulergine hydrochloride. GR 127935 showed a trend toward reducing myoclonus. Dose-response studies showed that all doses of methiothepin mesylate and the three highest doses of mesulergine hydrochloride inhibited myoclonus effectively.. 5-HT1B, 5-HT2A/2B, and possibly 5-HT1D receptor subtypes likely play a role in posthypoxic myoclonus. More specific 5-HT antagonists that affect these receptor subtypes are candidates for future testing in this model and in Lance-Adams syndrome.

Topics: Acoustic Stimulation; Animals; Brain Chemistry; Disease Models, Animal; Dose-Response Relationship, Drug; Ergolines; Heart Arrest; Hypoxia; Hypoxia, Brain; Male; Methiothepin; Myoclonus; Oxadiazoles; Piperazines; Rats; Rats, Sprague-Dawley; Receptors, Serotonin; Serotonin Antagonists

Effects of lisuride, a central dopamine agonist of the ergot type, on local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were studied using the autoradiographical 14C-iodoantipyrine and 3H-deoxyglucose method, respectively, in conscious rats. Lisuride significantly stimulated LCBF in the cerebellar gray matter. LCBF in some other regions including the cerebral cortex, caudate-putamen, thalamus, geniculate body and substantia nigra were also stimulated by lisuride. No changes were observed in the hippocampus, hypothalamus and white matter. A close correlation was observed between LCBF and LCGU. Region specificity of the stimulatory effect by lisuride on LCBF and LCGU was coincident. Lisuride shortened the lethal time in the anoxia model. In conclusion, lisuride stimulated not only glucose utilization but also blood flow in local regions of the brain.

Topics: Animals; Brain; Cerebrovascular Circulation; Ergolines; Female; Glucose; Hypoxia; Lisuride; Male; Mice; Microcirculation; Rats; Rats, Inbred Strains; Stimulation, Chemical

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

An increase in specific dopamine D2 receptor binding sites was observed in membranes prepared from the carotid bodies of rabbits treated for 8 weeks and then withdrawn for 4-9 days from the D2 antagonist domperidone (2-5 mg/kg per day). Recordings of chemoreceptor afferent discharge from the carotid body also revealed that this change in receptor density was accompanied by an increased sensitivity to the chemodepressant effects of exogenous dopamine. The chemoreceptor responsiveness of the carotid body to hypoxia is blunted in rabbits treated chronically with domperidone, but this can be restored to normal by an acute dose of the D2 antagonist. These experiments provide evidence that is compatible with a chemo-inhibitory role for endogenous dopamine in the rabbit's carotid body. Furthermore, these results suggest that the carotid body provides a useful model for the functional studies of dopamine D2 receptors.

Topics: Animals; Binding Sites; Carotid Body; Chemoreceptor Cells; Domperidone; Dopamine; Electrophysiology; Ergolines; Hypoxia; Male; Membranes; Neurons; Quinpirole; Rabbits; Receptors, Dopamine

Topics: Animals; Atmospheric Pressure; Ergolines; Hypoxia; Male; Nicergoline; Rats; Rats, Inbred Strains; Time Factors; Vinca Alkaloids; Vincamine

Topics: Animals; Atmospheric Pressure; Ergolines; Hypoxia; Male; Nicergoline; Rats

Topics: Adenosine Triphosphate; Adrenergic alpha-Antagonists; Anesthesia; Animals; Bemegride; Brain; Bromine; Carotid Arteries; Cocaine; Dipyridamole; Dogs; Electroencephalography; Energy Transfer; Ergolines; Femoral Artery; Hypoglycemia; Hypotension; Hypoxia; Lactates; Ligation; Male; Malonates; NAD; Nicotinic Acids; Pyruvates; Time Factors; Urethane

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Bemegride; Brain; Dogs; Energy Metabolism; Ergolines; Hypoxia; Hypoxia, Brain; Nicergoline; Oxygen Consumption