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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.


R Markstein. Hydergine: interaction with the neurotransmitter systems in the central nervous system. Journal de pharmacologie. 1985;16 Suppl 3:1-17

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PMID: 2869188

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