Eglumegad
Encyclopedia
Eglumegad 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.
/3
). Findings about a direct interaction on dopamine D2 receptors
are inconsistent.
for treating anxiety symptoms in several standard tests, but without producing any of the negative side effects of diazepam such as sedation and memory impairment. Tests in humans confirmed that it produced anxiolytic effects without producing sedation. However it did slightly reduce cognitive performance in tests on monkeys.
Eglumegad 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.
Eglumegad and related drugs are neuroprotective and are synergistic with the neuroprotection produced by 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 eglumegad 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 eglumegad may have potential uses in the treatment of some forms of psychosis, although eglumegad 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.
form LY544344 looks more likely to be the final candidate for aspired marketing.
Eli Lilly and Company
Eli Lilly and Company is a global pharmaceutical company. Eli Lilly's global headquarters is located in Indianapolis, Indiana, in the United States...
, which is being investigated for its potential in the treatment of anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
and drug addiction. It is a glutamate derived compound and its mode of action implies a novel mechanism.
Mechanism of action
Eglumegad acts as a group-selective agonist for the group II metabotropic glutamate receptors (mGluR2Metabotropic glutamate receptor 2
Metabotropic glutamate receptor 2 is a protein that in humans is encoded by the GRM2 gene.-PAMs:The development of subtype-2-selective positive allosteric modulators experienced steady advance in recent years...
/3
Metabotropic glutamate receptor 3
Metabotropic glutamate receptor 3 is a protein that in humans is encoded by the GRM3 gene.-Ligands:Though truly mGluR3 selective agents still await their discovery, mixed mGluR2/3 ligands with selectivity over other mGluR-subtypes are known...
). Findings about a direct interaction on dopamine D2 receptors
Dopamine receptor D2
Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene.- Function :This gene encodes the D2 subtype of the dopamine receptor. This G protein-coupled receptor inhibits adenylyl cyclase activity...
are inconsistent.
Effects
In experiments on mice, eglumegad was found to be as effective as diazepamDiazepam
Diazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...
for treating anxiety symptoms in several standard tests, but without producing any of the negative side effects of diazepam such as sedation and memory impairment. Tests in humans confirmed that it produced anxiolytic effects without producing sedation. However it did slightly reduce cognitive performance in tests on monkeys.
Eglumegad has also been found to be effective in relieving the symptoms of withdrawal from chronic use of both nicotine
Nicotine
Nicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves...
and morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
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.
Eglumegad and related drugs are neuroprotective and are synergistic with the neuroprotection produced by 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 eglumegad 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 eglumegad may have potential uses in the treatment of some forms of psychosis, although eglumegad had only limited effects on the action of the dissociative drug phencyclidine
Phencyclidine
Phencyclidine , commonly initialized as PCP and known colloquially as angel dust, is a recreational dissociative drug...
which is generally a better model for schizophrenia than the 5HT2A agonist hallucinogens.
Clinical development
Development of this drug is continuing, with several clinical trials completed and more planned. Poor oral bioavailability of the original formulation led to limited efficacy in the initial human trials, and so the prodrugProdrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
form LY544344 looks more likely to be the final candidate for aspired marketing.