Dihydroergotoxine, also known as hydergine, was developed by scientist Albert Hofmann for Sandoz Inc (now owned by Novartis). It is primarily indicated to treat dementia and age-related cognitive impairment, both idiopathic in nature as well as to supplement therapy for known diseases such as Alzheimer's. Sometimes dihydroergotoxine is indicated for use in recovery for stroke victims, also. Like many drugs indicated to treat, reverse, or prevent cognitive decline, dihydroergotoxine is also used by some individuals for nootropic or cognitive-enhancing benefits.
The primary mechanism of action of dihydroergotoxine and other ergoloids is unclear at the present time and does not resemble any other known class of drug. It acts as an agonist to dopaminergic and serotonergic receptors and an antagonist for alpha-adrenoreceptors. Hydergine modulates synaptic neurotransmitter levels as well as increasing blood flow to the brain; at one time, it was believed that the latter mechanism was the primary mode of action by which dihydroergotoxine provides beneficial effects..
In one study in rats, activity due to hydergine treatment was observed in the hypothalamus, hippocampus and cerebellum. The observed hydergine effect was more pronounced in the aged group in the hypothalamus and cerebellum, and more pronounced in the younger adults in the hippocampus. This may be due to MAO activity, which increases with age, and which dihydroergotoxine may modulate, thereby mimicking more "youthful" brain activity patterns.
At least one clinician feels that dihydroergotoxine may be a logical treatment for depression in the elderly, which often has different chemical causes in the brain than that of younger people; dihydroergotoxine would act as a sort of MAO inhibitor with selective activity and additional cognitive benefits over traditional MAOIs.
Studies using recommended or indicated doses of dihydroergotoxine have often shown it to be less effective than animal model studies, which led researchers to speculate that perhaps the dose for humans ought to be higher than that currently indicated; at least study supported this conclusion.
Finally, regarding higher-than-"normal" doses, Hindmarch et al found:
Hydergine, 12 mg per day for two weeks, has some direct activity on a variety of tasks of mental and cognitive performance. These results add support to biochemical findings that implicate the ergot alkaloids (particularly co-dergo-crine, Hydergine) in cellular activity likely to increase cortical arousal and awareness. The high dose of Hydergine used in this volunteer study was exceptionally well tolerated and did produce significant results on individual measures of central nervous system activity which might suggest the use of similar doses in patient populations. The findings of a hangover of activity after drug withdrawal and the fact that some CNS activity (serial subtraction of 17s) is not obvious until two weeks of medication would suggest the need for pharmacokinetic measures to be taken in conjunction with psychologic assessments. It would seem that a two-week schedule of repeated doses is the minimum required to produce an effect on CNS activity, but even with such a dose regimen it appears that the drug continues to exert some effect after its withdrawal.
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Büyüköztürk A, Kanit L, Ersöz B, Menteş G, Hariri NI. The effects of hydergine on the MAO activity of the aged and adult rat brain. Eur Neuropsychopharmacol. 1995 Dec;5(4):527-9.
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Hindmarch I, Parrott AC, Lanza M.J Clin Pharmacol. The effects of an ergot alkaloid derivative (Hydergine) on aspects of psychomotor performance, arousal, and cognitive processing ability. 19(11-12):726-32. 1979.
*The latter article is intended for educational / informational purposes only. THIS PRODUCT IS INTENDED AS A RESEARCH CHEMICAL ONLY. This designation allows the use of research chemicals strictly for in vitro testing and laboratory experimentation only. Bodily introduction of any kind into humans or animals is strictly forbidden by law.