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Relmada Therapeutics, Inc.

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  • The novel uncompetitive NMDA receptor antagonist esmethadone has no meaningful abuse potential in recreational drug users

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  • REL-1017 (esmethadone) as adjunctive treatment in patients with major depressive disorder: a phase 2 randomized double-blind trial

    View publication

  • Subanalysis of subjective cognitive measures from a phase 2, double-blind, randomized trial of REL-1017 in patients with major depressive disorder

    View publication

  • Esmethadone‐HCl (REL‐1017): a promising rapid antidepressant

    View publication

  • Efficacy and Safety of Esmethadone (REL-1017) in Patients With Major Depressive Disorder and Inadequate Response to Standard Antidepressants: A Phase 3 Randomized Controlled Trial

    View poster

  • No Indication of Abuse Potential and Absence of Withdrawal Signs and Symptoms From Esmethadone (REL-1017): Results From a Phase 3 Randomized Controlled Trial in Patients With Major Depressive Disorder

    View poster

  • Esmethadone (REL-1017) compares with NMDA receptor antagonists in FLIPR-calcium assay

    View publication View poster

  • REL-1017 (esmethadone hydrochloride), a potential rapid-acting antidepressant has no meaningful opioid abuse potential in non-clinical and clinical abuse potential studies

    View poster

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

    View publication

  • No meaningful abuse potential in recreational ketamine users of REL-1017 (esmethadone hydrochloride), a new NMDAR antagonist and potential rapid-acting antidepressant

    View poster

  • REL-1017 (esmethadone hydrochloride) demonstrates neither toxic effects on maternal health nor teratogenic effects in pregnant rats

    View poster

  • REL-1017 (esmethadone) increases circulating BDNF levels in healthy subjects of a phase 1 clinical study

    View publication

  • 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

    View publication

  • No meaningful abuse potential in recreational opioid users of REL-1017 (esmethadone hydrochloride), a new NMDAR antagonist and potential rapid-acting antidepressant

    View poster

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

    View publication

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

    View publication

  • REL-1017 (esmethadone hydrochloride) a novel uncompetitive NMDAR antagonist with a preference for NR1-NR2D subtypes shows rapid, robust and sustained rapid antidepressant effects as adjunctive treatment for Major Depressive Disorder

    View poster

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

    View publication View poster

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

    View publication

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

    View publication

  • Esmethadone (REL-1017) blocks NMDA receptors and reduces Ca2+ entry in presence of quinolinic acid and gentamicin

    View publication View poster

  • REL-1017 (esmethadone) showed no reinforcing properties compared to oxycodone in a rat self-administration study

    View poster

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

    View publication

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

    View publication

  • REL-1017 (esmethadone) demonstrates no physical dependence and no withdrawal effects in a rat study

    View poster

  • No meaningful abuse potential in recreational opioid users of REL-1017 (esmethadone hydrochloride), a new NMDAR antagonist and potential rapid-acting antidepressant

    View poster

  • No meaningful abuse potential in recreational ketamine users of REL-1017 (esmethadone hydrochloride), a new NMDAR antagonist and potential rapid-acting antidepressant

    View poster

  • Case report: REL-1017 reduces abnormal Clinician Administered Dissociative States Scale scores in patients with major depressive disorder

    View publication View poster

  • A Phase 2a double-blind randomized trial of REL-1017 (esmethadone) in patients with major depressive disorder: Analysis of subscales from the Symptoms of Depression Questionnaire

    View publication View poster

  • Effect of REL-1017 (esmethadone) on cholesterol, triglycerides, PCSK9 and hs-CRP in patients with major depressive disorder

    View publication View poster

  • Effect of percentage of life-years from the start of major depressive disorder on the therapeutic response to REL-1017

    View poster

  • Esmethadone (REL-1017) reduces glutamate-induced currents in NMDA receptors with the GluN2D subunit

    View publication View poster

  • Esmethadone (REL-1017) reduces NMDA receptor currents in a concentration dependent manner

    View poster

  • Esmethadone (REL-1017) shows slower onset kinetics compared to ketamine in manual patch clamp studies

    View publication View poster

  • Esmethadone (REL-1017) restores NMDA receptor 1 subunit expression in an in vitro model of glutamatergic excitotoxicity

    View publication View poster

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

    View publication

Published articles

The novel uncompetitive NMDA receptor antagonist esmethadone has no meaningful abuse potential in recreational drug users

Shram M, Henningfield J, Apseloff G, Gorodetzky C, Martin S, Vocci F, Sapienza F, Kosten T, Huston J, Buchhalter A, Ashworth J, Lanier R, Folli F, Mattarei A, Guidetti C, Comai S, O'Gorman C, Traversa S, Inturrisi C, Manfredi P, Pappagallo M

Transl Psychiatry 13, 192 (2023)

https://www.nature.com/articles/s41398-023-02473-8

Published articles

REL-1017 (esmethadone) as adjunctive treatment in patients with major depressive disorder: a phase 2 randomized double-blind trial

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

Am J Psychiatry. 2022 Feb;179(2):122-131.

doi: 10.1176/appi.ajp.2021.21020197 Epub 2021 Dec 22

Published articles

Subanalysis of subjective cognitive measures from a phase 2, double-blind, randomized trial of REL-1017 in patients with major depressive disorder

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

Prim Care Companion CNS Disord. 2023;25(1):22m03267.

https://doi.org/10.4088/PCC.22m03267

Published articles

Esmethadone‐HCl (REL‐1017): a promising rapid antidepressant

Fava M, Stahl S, De Martin S, Mattarei A, Bettini E, Comai S, Alimonti A, Bifari F, Pani L, Folli F, Guidetti C, Furlan A, Sgrignani J, Locatelli P, Cavalli A, O’Gorman C, Traversa S, Inturrisi C, Pappagallo M, Manfredi P

Eur Arch Psychiatry Clin Neurosci. 2023.

https://link.springer.com/article/10.1007/s00406-023-01571-4

Congress presentations

Efficacy and Safety of Esmethadone (REL-1017) in Patients With Major Depressive Disorder and Inadequate Response to Standard Antidepressants: A Phase 3 Randomized Controlled Trial

Fava M , Stahl SM , Pani L , Bushnell D, O’Gorman C, De Martin S, Guidetti C, Mattarei A, Comai S , Folli F, Traversa S , Inturrisi CE , Manfredi PL, Pappagallo M

American Society of Clinical Psychopharmacology (ASCP) 2023

View poster

Congress presentations

No Indication of Abuse Potential and Absence of Withdrawal Signs and Symptoms From Esmethadone (REL-1017): Results From a Phase 3 Randomized Controlled Trial in Patients With Major Depressive Disorder

Shram M , Henningfield J , Gorodetzky C, De Martin S, Vocci F, Sapienza F, Kosten T, Bushnell D, Guidetti C, O’Gorman C, Folli F, Traversa S, Inturrisi CE, Manfredi PL, Pappagallo M

American Society of Clinical Psychopharmacology (ASCP) 2023

View poster

Congress presentations

Esmethadone (REL-1017) compares with NMDA receptor antagonists in FLIPR-calcium assay

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

Society of Biological Psychiatry (SOBP) Annual Meeting 2021.

Biological Psychiatry. 2021;89(9), S294.

View poster https://doi.org/10.1016/j.biopsych.2021.02.732

Congress presentations

REL-1017 (esmethadone hydrochloride), a potential rapid-acting antidepressant has no meaningful opioid abuse potential in non-clinical and clinical abuse potential studies

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

The College of Problems of Drug Dependence (CPDD) 2022.

View poster

Published articles

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

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

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

https://doi.org/10.1097/JCP.0000000000001583

Congress presentations

No meaningful abuse potential in recreational ketamine users of REL-1017 (esmethadone hydrochloride), a new NMDAR antagonist and potential rapid-acting antidepressant

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

American Society of Clinical Psychopharmacology (ASCP) 2022.

View poster

Congress presentations

REL-1017 (esmethadone hydrochloride) demonstrates neither toxic effects on maternal health nor teratogenic effects in pregnant rats

Bifari F, Pappagallo M, Folli F, Manfredi M

Society of Biological Psychiatry (SOBP) Annual Meeting 2022.

View poster

Published articles

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

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

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

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

Published articles

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

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

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

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

Congress presentations

No meaningful abuse potential in recreational opioid users of REL-1017 (esmethadone hydrochloride), a new NMDAR antagonist and potential rapid-acting antidepressant

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

Ketamine 2022.

View poster

Published articles

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

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

Pharmaceuticals 2022;15(8):997.

https://doi.org/10.3390/ph15080997

Published articles

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

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

Pharmaceuticals. 2022;15 (7), 882.

https://doi.org/10.3390/ph15070882

Congress presentations

REL-1017 (esmethadone hydrochloride) a novel uncompetitive NMDAR antagonist with a preference for NR1-NR2D subtypes shows rapid, robust and sustained rapid antidepressant effects as adjunctive treatment for Major Depressive Disorder

Pappagallo M & Manfredi P

Ketamine 2022.

View poster

Congress presentations

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

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

American College of Neuropsychopharmacology (ACNP) 60th Annual Meeting 2021.

Neuropsychopharmacol. 46, 218-368, P315 (2021).

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

Published articles

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

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

Scientific Reports. 2022;12,11389.

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

Published articles

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

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

Frontiers in Pharmacology. 2022. 13:863959.

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

Congress presentations

Esmethadone (REL-1017) blocks NMDA receptors and reduces Ca2+ entry in presence of quinolinic acid and gentamicin

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

Society of Biological Psychiatry (SOBP) Annual Meeting 2021.

Biological Psychiatry. 2021;89(9), S198.

View poster https://doi.org/10.1016/j.biopsych.2021.02.502

Congress presentations

REL-1017 (esmethadone) showed no reinforcing properties compared to oxycodone in a rat self-administration study

Henningfield J, Gauvin D, Bifari F, Fant R, Buchhalter A, Ashworth J, Lanier R, Caron J, Pappagallo M, Folli F, Manfredi P

The College on Problems of Drug Dependence (CPDD) Annual Meeting 2021.

View poster

Published articles

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

Hanania T, Manfredi P, Inturrisi C, Vitolo O

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

https://doi.org/10.1037/pha0000310

Published articles

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

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

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

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

Congress presentations

REL-1017 (esmethadone) demonstrates no physical dependence and no withdrawal effects in a rat study

Gauvin D, Henningfield J, Bifari F, Fant R, Buchhalter A, Ashworth J, Lanier R, Caron J, Pappagallo M, Folli F, Manfredi P

The College on Problems of Drug Dependence (CPDD) Annual Meeting 2021.

View poster

Congress presentations

No meaningful abuse potential in recreational opioid users of REL-1017 (esmethadone hydrochloride), a new NMDAR antagonist and potential rapid-acting antidepressant

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

American Society of Clinical Psychopharmacology (ASCP) 2022.

View poster

Congress presentations

No meaningful abuse potential in recreational ketamine users of REL-1017 (esmethadone hydrochloride), a new NMDAR antagonist and potential rapid-acting antidepressant

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

Ketamine 2022.

View poster

Congress presentations

Case report: REL-1017 reduces abnormal Clinician Administered Dissociative States Scale scores in patients with major depressive disorder

Guidetti C, Pani L, Fava M, Pappagallo M, Serra G, De Martin S, Folli F, Manfredi P

Neuroscience Education Institute (NEI) 2021.

CNS Spectrums, Volume 27, Issue 2, April 2022, pp. 236.

View poster https://doi.org/10.1017/S1092852922000360

Congress presentations

A Phase 2a double-blind randomized trial of REL-1017 (esmethadone) in patients with major depressive disorder: Analysis of subscales from the Symptoms of Depression Questionnaire

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

Neuroscience Education Institute (NEI) 2021.

CNS Spectrums, Volume 27, Issue 2, April 2022, pp. 235.

View poster https://doi.org/10.1017/S1092852922000359

Congress presentations

Effect of REL-1017 (esmethadone) on cholesterol, triglycerides, PCSK9 and hs-CRP in patients with major depressive disorder

Ferri N, Pappagallo M, Patel S, Folli F, De Martin S, Lupo MG, Traversa S, Manfredi PL

Neuroscience Education Institute (NEI) 2021.

CNS Spectrums, Volume 27, Issue 2, April 2022, pp. 246 – 247.

View poster https://doi.org/10.1017/S1092852922000578

Congress presentations

Effect of percentage of life-years from the start of major depressive disorder on the therapeutic response to REL-1017

Fava M, Pani L, De Martin S, Pappagallo M, Manfredi P

American Psychiatric Association (APA) Annual Meeting 2021.

View poster

Congress presentations

Esmethadone (REL-1017) reduces glutamate-induced currents in NMDA receptors with the GluN2D subunit

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

Society of Biological Psychiatry (SOBP) Annual Meeting 2021.

Biological Psychiatry. 2021;89(9), S198-S199.

View poster https://doi.org/10.1016/j.biopsych.2021.02.503

Congress presentations

Esmethadone (REL-1017) reduces NMDA receptor currents in a concentration dependent manner

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

Society of Biological Psychiatry (SOBP) Annual Meeting 2021.

View poster

Congress presentations

Esmethadone (REL-1017) shows slower onset kinetics compared to ketamine in manual patch clamp studies

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

Society of Biological Psychiatry (SOBP) Annual Meeting 2021.

Biological Psychiatry. 2021;89(9), S294-S295.

View poster https://doi.org/10.1016/j.biopsych.2021.02.733

Congress presentations

Esmethadone (REL-1017) restores NMDA receptor 1 subunit expression in an in vitro model of glutamatergic excitotoxicity

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

Society of Biological Psychiatry (SOBP) Annual Meeting 2021.

Biological Psychiatry. 2021;89(9), S383-S384.

View poster https://doi.org/10.1016/j.biopsych.2021.02.953

Published articles

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

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

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

https://doi.org/10.3390/ijms232012196

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