title: Interaction of ergot alkaloids and their combination (co-dergocrine) with alpha-adrenoceptors in the CNS.
abstract: Co-dergocrine (Hydergine), composed of four dihydrogenated peptide ergot alkaloids (dihydroergocornine, dihydroergocristine, dihydro-alpha-ergokryptine and dihydro-beta-ergokryptine), has been reported to interact with alpha-adrenoceptors. The effect of the combination and its individual components on alpha-adrenoceptors subtypes in the rat brain was investigated in the present study. All five ergot drugs displaced [3H]rauwolscine, [3H]clonidine and [3H]WB 4101 from specific binding sites in membrane preparations from rat and bovine brain at nanomolar concentrations. In rat cerebral occipital cortex slices, the ergot drugs inhibited 1-noradrenaline-stimulated cyclic AMP formation (alpha 1-adrenoceptor test) and facilitated electrically evoked noradrenaline release (alpha 2-adrenoceptor test) at nanomolar concentrations. The results from the functional tests suggest that the ergot drugs have a slightly higher affinity to alpha 2-adrenoceptors which are antagonised in a competitive manner. The alpha 1-adrenoceptors are antagonised by the ergot drugs in a non-competitive manner. The relative order of potency at both receptor types was similar in that dihydroergocornine, dihydro-alpha-ergokryptine and dihydro-beta-ergokryptine were equipotent, whereas dihydroergocristine was less potent. The effect of the combination of the ergot alkaloids at both alpha-adrenoceptors appears to reflect the summation of the contributions of its components. The differences seen in the functional tests were less pronounced in the binding tests.
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003000:Clonidine / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004088:Dihydroergotoxine / Q000494:pharmacology*; D004146:Dioxanes / Q000378:metabolism; D004338:Drug Combinations; D004876:Ergot Alkaloids / Q000494:pharmacology*; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D015016:Yohimbine / Q000378:metabolism
chemical_list: D004146:Dioxanes; D004338:Drug Combinations; D004876:Ergot Alkaloids; D011942:Receptors, Adrenergic, alpha; D004088:Dihydroergotoxine; D015016:Yohimbine; D000242:Cyclic AMP; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D003000:Clonidine; D009638:Norepinephrine