Data and publications

Published articles

Fava M, Stahl S, Pani L, De Martin S, Pappagallo M, Guidetti C, Alimonti A, Bettini E, Mangano RM, Wessel T, de Somer M, Caron J, Vitolo OV, DiGuglielmo G, Gilbert A, Mehta H, Kearney M, Mattarei A, Gentilucci M, Folli F, Traversa S, Inturrisi C, Manfredi P

REL-1017 (Esmethadone) as adjunctive treatment in patients with major depressive disorder: a phase2a randomized double-blind trial

Am J Psychiatry. 2022 Feb;179(2):122-131.
doi: 10.1176/appi.ajp.2021.21020197 Epub 2021 Dec 22

Guidetti C, Serra G, Pani L, Pappagallo M, Maglio G, Trasolini M, De Martin S, Mattarei A, Bifari G, Folli F, Manfredi P, Fava M

REL-1017 (Esmethadone) may rapidly reduce dissociative symptoms in adults with major depressive disorder unresponsive to standard antidepressants: a report of 2 cases

Journal of Clinical Psychopharmacology. 2022;10.1097/JCP.0000000000001583.

De Martin S, Gabbia D, Folli F, Bifari F, Fiorina P, Ferri N, Stahl S, Inturrisi C, Pappagallo M, Traversa S, Manfredi P

REL-1017 (Esmethadone) increases circulating BDNF levels in healthy subjects of a Phase 1 clinical study

Frontiers in Pharmacology. 2021;12:973-978.

Bernstein G, Davis K, Mills C, Wang L, McDonnell M, Oldenhof J, Inturrisi C, Manfredi P, Vitolo O

Characterization of the safety and pharmacokinetic profile of d-methadone, a novel N-methyl-D-aspartate receptor antagonist in healthy, opioid-naive subjects: Results of two Phase 1 studies

Journal of Clinical Psychopharmacology. 2019;39(3):226-237.

Stahl S, De Martin S, Mattarei A, Bettini E, Pani L, Guidetti C, Folli F, de Somer M, Traversa S, Inturrisi C, Pappagallo M, Gentilucci M, Alimonti A, Fava M, and Manfredi P

Esmethadone (REL-1017) and other uncompetitive NMDAR channel blockers may improve mood disorders via modulation of synaptic kinase-mediated signaling

Int. J. Mol. Sci. 2022; 23(20), 12196.

Bettini E, Stahl S, De Martin S, Mattarei A, Sgrignani J, Carignani C, Nola S, Locatelli P, Pappagallo M, Inturrisi C, Bifari F, Cavalli A, Alimonti A, Pani L, Fava M, Traversa S, Folli F, Manfredi P

Pharmacological comparative characterization of REL-1017 (Esmethadone-HC1) and other NMDAR channel blockers in human heterodimeric N-Methyl-D-Aspartate receptors

Pharmaceuticals 2022;15(8):997.

Bettini E, De Martin S, Mattarei A, Pappagallo M, Stahl S, Bifari F, Inturrisi C, Folli F, Traversa S, Manfredi P

The N-Methyl-D-Aspartate receptor blocker REL-1017 (Esmethadone) reduces calcium influx induced by glutamate, quinolinic acid and gentamicin

Pharmaceuticals. 2022;15 (7), 882.

Henningfield J, Gauvin D, Bifari F, Fant R, Shram M, Buchhalter A, Ashworth J, Lanier R, Pappagallo M, Inturrisi C, Folli F, Traversa S, Manfredi P

REL-1017 (Esmethadone, D-methadone) does not cause reinforcing effect, physical dependence and withdrawal signs in Sprague Dawley rats

Scientific Reports. 2022;12,11389.

Bifari F, Pappagallo M, Bleavins M, Traversa S, Folli F, Manfredi P

REL-1017 (Esmethadone), a novel NMDAR blocker for the treatment of MDD is not neurotoxic in Sprague-Dawley rats

Frontiers in Pharmacology. 2022. 13:863959.

Hanania T, Manfredi P, Inturrisi C, Vitolo O

The N-methyl-D-aspartate receptor antagonist d-methadone acutely improves depressive-like behavior in the forced swim test performance of rats

Exp Clin Psychopharmacol. 2020;28(2):196-201.

Fogaça M, Fukumoto K, Franklin T, Liu R, Duman C, Vitolo O, Duman R

N-methyl-D-aspartate receptor antagonist d-methadone produces rapid, mTORC1-dependent antidepressant effects

Neuropsychopharmacology. 2019;44(13):2230-2238.

Congress presentations

Henningfield J, Apseloff G, Gorodetzky C, Pappagallo M, Shram M, De Martin S, Fant R, Vocci F, Sapienza F, Kosten T, Huston J, Buchhalter A, Ashworth J, Lanier R, Folli F, Traversa S, Inturrisi C, Manfredi P

No meaningful opioid abuse liability of REL-1017 (esmethadone; d-methadone), a rapid-acting antidepressant in clinical development: a human abuse potential study

American College of Neuropsychopharmacology (ACNP) 60th Annual Meeting 2021.
Neuropsychopharmacol. 46, 218-368, P315 (2021).