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Eglumetad (), also known as eglumegad and by its developmental code name LY-354740, is a research drug developed by Eli Lilly and Company, which is being investigated for its potential in the treatment of anxiety and drug addiction. It is a glutamate derived compound and its mode of action implies a novel mechanism.
Eglumetad has also been found to be effective in relieving the symptoms of withdrawal from chronic use of both nicotine and morphine in animals, as well as inhibiting the development of tolerance to morphine, raising hope that this drug may be useful for treating drug addiction in humans.
Eglumetad and related drugs are neuroprotective and are synergistic with the neuroprotection produced by N-Methyl-D-aspartic acid (NMDA) antagonist drugs, which may make these drugs useful in aiding recovery from brain injury.
This class of drugs also interacts with hallucinogenic drugs, with eglumetad reducing the effects of 5HT2A agonist hallucinogens, while conversely the mGluR2/3 antagonist LY341495 increased the behavioural effects of these drugs. This suggests that mGluR2/3 agonists such as eglumetad may have potential uses in the treatment of some forms of psychosis, although eglumetad had only limited effects on the action of the dissociative drug phencyclidine which is generally a better model for schizophrenia than the 5HT2A agonist hallucinogens.
Eglumetad also interferes in the hypothalamic–pituitary–adrenal axis, with chronic oral administration of this drug leading to markedly reduced baseline cortisol levels in bonnet macaques (Macaca radiata); acute infusion of eglumetad resulted in a marked diminution of yohimbine-induced stress response in those animals.
In human Adrenal cortex, eglumetad has been shown to down-regulate intracellular cyclic AMP (cAMP) and steroidogenesis, with a significant decrease in aldosterone and cortisol production.
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