Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00711 (Hydergine)
 115 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hydergine (co-dergocrine, ergoloid mesylates, dihydroergotoxine) is an ergot preparation which has been shown to be of value in the treatment of senile mental impairment. Results from biochemical in vitro investigations suggest that Hydergine interacts directly with subtypes of alpha-adrenoceptors, dopamine and serotonin receptors. For instance, in slices of rat cerebral cortex, it blocked noradrenaline-induced increase of cyclic AMP content and facilitated electrically evoked noradrenaline release which is consistent with antagonistic properties at postsynaptic alpha 1- and presynaptic alpha 2-adrenoceptors. Furthermore, Hydergine had mixed agonist/antagonist properties at postsynaptic D1 receptors mediating stimulation of adenylate cyclase, and at pre- and postsynaptic D2 receptors mediating inhibition of evoked dopamine and acetylcholine release in the rat striatum, respectively. Hydergine had also mixed agonist/antagonist properties at the serotonin-sensitive adenylate cyclase in the rat hippocampus and the presynaptic serotonin autoreceptors present on nerve terminals in the rat cortex. Based on these in vitro data, it is suggested that Hydergine influences central monoaminergic systems in a dualistic manner. On the one hand, it can compensate for a transmitter deficit in dopaminergic and serotoninergic systems, but at the same time, counteract a possible hyperactivity in the same transmitter systems. The noradrenergic systems may be affected in a similar way but by a different mechanism. In this latter system, Hydergine increased evoked noradrenaline release by blocking presynaptic alpha-adrenergic autoreceptors, but by a simultaneous blockade of postsynaptic alpha 1-adrenoceptors sets a ceiling effect to the noradrenergic stimulation. Thus, Hydergine might be able to counteract and prevent disturbances in the interplay between monoaminergic and other transmitter systems in the central nervous system. It is proposed that these multiple effects of Hydergine are in part responsible for its beneficial effects in senile mental impairment.
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PMID:Hydergine: interaction with the neurotransmitter systems in the central nervous system. 286 88

Co-dergocrine (Hydergine), an ergot preparation composed of four dihydrogenated peptide ergot alkaloids (dihydroergocornine, dihydroergocristine, dihydro-alpha-ergokryptine, dihydro-beta-ergokryptine, 3:3:2:1), has been reported to exert in vivo effects suggesting an interaction with dopaminergic systems. The present investigation provides evidence that, in the striatum of the rat, co-dergocrine and its components interact directly with D1- and D2-subtypes of dopamine receptors. In homogenates of rat striatum, co-dergocrine and three of its components (dihydroergocornine, dihydro-alpha-ergokryptine, dihydro-beta-ergokryptine) stimulate cyclic AMP formation (D1-receptor response) having similar EC50 values but different efficacies. The same compounds inhibit electrically evoked tritium overflow from rat striatal slices preincubated with [3H]choline (D2-receptor response) at about 50 times lower concentrations. Here again the compounds exhibit differential maximal effects. One component, dihydroergocristine, antagonises both receptor types. The effect of co-dergocrine in functional responses mediated by both D1- and D2-receptors seems to reflect the summation of the contribution of its components.
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PMID:Dopamine receptor profile of co-dergocrine (Hydergine) and its components. 629 30

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.
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PMID:Interaction of ergot alkaloids and their combination (co-dergocrine) with alpha-adrenoceptors in the CNS. 631 49