Hydergine: Interaction with Neurotransmitter Systems in the Central Nervous System
Hydergine (co-dergocrine, ergoloid mesylates, dihydroergotoxine) is an ergot preparation shown to be of value in the treatment of senile mental impairment.
Inexperimental animals, Hydergine induces behaviors suggesting an influence on monoaminergic systems. Results from biochemical in vitro studies indicate that Hydergine has multiple effects and interacts directly with α-adrenoceptors, dopamine (DA), and serotonin (5-TH) receptor subtypes. In rat cortex slices, it blocks noradrenaline (NA)-induced cyclic adenosine monophosphate (cAMP) formation and facilitates evoked NA release. This indicates antagonistic effects at α 1 - and α 2 - adrenoceptors. Furthermore, Hydergine has mixed agonistic/antagonistic effects at postsynaptic DA receptors, stimulating adenylate cyclase and inhibiting action-potential-evoked acetylcholine release in the rat striatum. Also, at presynaptic DA receptors inhibiting evoked DA release in the rat striatum, Hydrergine has mixed agonistic/antagonistic effects.
Moreover, Hydergine was found to have mixed agonistic/antagonistic effects on 5-HT receptors involved in stimulating adenylate cyclase activity in homogenates of rat hippocampus. In slices of rat hippocampus, Hydergine enhanced electrically evoked acetylcholine release. Based on these findings, it is suggested that Hydergine can various transmitter systems in the central nervous system.
KeywordsAdenylate Cyclase Ergot Alkaloid Monoaminergic System Cortex Slice Tritium Overflow
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