Repurposing of Known Metabolites to Treat Anxiety and Depression

Categories: “Neurological Disorders

Reference: #2010-048

OTC Contact: Ruchika Nijhara, Ph.D., MBA, CLP ( Directory Information | Send a Message )


Anxiety and depression are the two most common mental health disorders in the United States, and while treatment of these disorders has improved, there is an unmet need for new anxiolytic and anti-depressant therapeutics. Current treatment strategies, such as selective monoaminergic reuptake inhibitors, are not effective in up to one third of patients, and adverse side effects of these drugs can be limiting. Recently, nicotinic acetylcholine receptors (nAChRs) have emerged as potential targets for a new class of anxiolytic/anti-depressant drugs.

Georgetown University scientists have shown that EMDP and EDDP, the primary metabolites of methadone, are efficacious in animal models of depression and anxiety. Unlike methadone, EMDP and EDDP do not modulate opioid receptors, and instead efficiently block α3β4 and α4β2 nAChRs. These compounds are likely safe for human use, are effective at physiological doses in vivo, have established clinical assays for regulatory purposes, and demonstrate similar results to mecamylamide, without the mecamylamide-associated side effects. 


Stage of Development

In vivo proof of concept data available

Relevant Publications

Forcelli P, Turner JR, Lee BG, Olson TT, Xie T, Xiao Y, Blendy JA, Kellar KJ. Anxiolytic- and Antidepressant-like Effects of the Methadone Metabolite 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP). Neuropharmacology, 101: 46 – 56, 2016

Patent Status

Patent application filed


Kenneth Kellar, Yingxian Xiao, Patrick Forcelli