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.
https://doi.org/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.
https://doi.org/10.3389/fphar.2021.671859

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.
https://doi.org/10.1097/jcp.0000000000001035

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.
https://doi.org/10.3390/ph15080997

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.
https://doi.org/10.3390/ph15070882

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.
https://doi.org/10.1038/s41598-022-15055-3

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.
https://doi.org/10.3389/fphar.2022.863959

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.
https://doi.org/10.1037/pha0000310

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.
https://doi.org/10.1038/s41386-019-0501-x

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).
https://doi.org/10.1038/s41386-021-01237-6