Esmethadone: the next breakthrough for patients with Major Depressive Disorder
Esmethadone (REL-1017) is an investigational compound. Safety and efficacy have not been established, and no regulatory authority has approved this product for any indication. Statements herein reflect interpretations of published or presented data.
Esmethadone is a potentially safe and well tolerated oral NMDAR antagonist in development for the adjunctive treatment of MDD
Esmethadone (REL-1017) is a novel circuit- and region-specific NMDAR antagonist selective for hyperactive GluN2D-containing subtypes. Esmethadone is under development as a rapid acting, adjunctive, once-daily, oral antidepressant for patients with inadequate response to first line therapy.
Esmethadone has completed Phase 1, Phase 2 and Phase З clinical trials, totaling over 1000 individual patient exposures. Across all trials, esmethadone was safe and well tolerated, with no meaningful opioid-like effects, ketamine-like effects or abuse liability, confirming results from studies utilizing state of the art preclinical models indicating lack of meaningful abuse potential.
The development of REL-1017 (esmethadone) is at a turning point
The esmethadone technology, co-invented by Drs. Inturrisi and Manfredi, was returned by Relmada Therapeutics to the original inventors on July 7, 2025. Drs. Inturrisi and Manfredi granted Levomecor Inc. a perpetual, worldwide, exclusive license to the esmethadone program.
With a patient-centered vision, the Levomecor team is fully focused on preparing the esmethadone program for NDA readiness.
Strong support from the scientific and medical community
The scientific community is strongly supportive of the esmethadone program. The esmethadone literature is authored by renowned experts.
There is an urgent medical need for novel rapid acting safe and well tolerated oral adjunctive antidepressant for patients with MDD who do not respond to first line therapy. Esmethadone may be particularly effective in subgroups of patients with refractory MDD.