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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

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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 2a randomized double-blind trial

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Pharmacokinetics, tolerability, and safety of esmethadone in subjects with chronic kidney disease or hepatic impairment

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
Sex-dependent effects of the uncompetitive N-methyl-D-aspartate receptor antagonist REL-1017 in G93A-SOD1 amyotrophic lateral sclerosis mice

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

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

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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

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Drug–drug interaction studies of esmethadone (REL‐1017) involving CYP3A4‐ and CYP2D6‐mediated metabolism

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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, d-methadone) does not cause reinforcing effect, physical dependence and withdrawal signs in Sprague Dawley rats

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

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

View publication
Letter to the Editor regarding ‘Unique pharmacodynamic properties and low abuse liability of the µ-opioid receptor ligand (S)-methadone’

View publication
Effect of time from onset of major depressive disorder on the therapeutic response to esmethadone (REL-1017)

View publication
N-methyl-D-aspartate receptors and depression: linking psychopharmacology, pathology and physiology in a unifying hypothesis for the epigenetic code of neural plasticity

View publication
Semaglutide and psilocybin in a mouse model of obesity, steatotic liver disease and type 2 diabetes

View poster
N-Methyl-D-Aspartate receptor uncompetitive antagonists and depression, from psychopharmacology and pathology to physiology: a unifying hypothesis for the epigenetic code of neural plasticity

View poster
Esmethadone (REL-1017) improves cognition in patients with severe major depressive disorder and inadequate response to standard antidepressants: a post hoc analysis from a Phase 3 randomized controlled trial

View poster
Depression severity and efficacy outcomes: post hoc analyses from a Phase 3 trial of the novel NMDAR antagonist antidepressant candidate esmethadone for the adjunctive treatment for MDD with inadequate response to standard antidepressants

View poster
Chronic non-psychedelic psilocybin therapy promotes visual rehabilitation in mice post-occipital stroke

View poster
Long-term safety and efficacy of esmethadone in patients with major depressive disorder: findings from a 12-Month open-label study

View poster
No indication of abuse or withdrawal potential with esmethadone (REL-1017): results from two Phase 3 randomized placebo-controlled trials in patients with major depressive disorder

View poster
Efficacy and safety of esmethadone (REL-1017) in patients with major depressive disorder and inadequate response to standard antidepressants: a Phase 3 randomized placebo-controlled trial

View poster
The serotonin receptor agonist psilocybin as a novel therapeutic approach for NAFLD: preclinical studies

View poster
Behavioral effects of a 14-day repeated treatment with psilocybin at a low non-psychedelic dose: a preliminary study in C57BL/6J mice

View poster
Efficacy of esmethadone (REL-1017) in patients with major depressive disorder and antidepressant tolerance (antidepressant tachyphylaxis)

View poster
No indication of abuse potential and absence of withdrawal from esmethadone (REL-1017) in patients with major depressive disorder

View poster
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

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

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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

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

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

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

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

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

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

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

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

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

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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

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

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

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

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

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

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

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

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

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Published articles

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 S, Pani L, De Martin S, Cutler A, Maletic V, Gorodetzky C, Vocci F, Sapienza F, Kosten T, Kröger C, Champasa P, O’Gorman C, Guidetti C, Alimonti A, Comai S, Mattarei A, Folli D, Bushnell D, Traversa S, Inturrisi C, Manfredi P, Pappagallo M

J Clin Psychiatry. 2024;85(3):24m15265.

DOI: 10.4088/JCP.24m15265

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. 2023 Jun 7;13(1):192.

DOI: 10.1038/s41398-023-02473-8

Published articles

REL-1017 (esmethadone) as adjunctive treatment in patients with major depressive disorder: a Phase 2a 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

Published articles

Pharmacokinetics, tolerability, and safety of esmethadone in subjects with chronic kidney disease or hepatic impairment

Ferri N, De Martin S, Stuart J, Traversa S, Mattarei A, Comai S, Folli F, Pappagallo M, Guidetti C, Inturrisi C, Manfredi P

Drugs R D. 2024 Jun;24(2):341-352.

DOI: 10.1007/s40268-024-00477-3

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 Feb 14;25(1):22m03267.

DOI: 10.4088/PCC.22m03267

Published articles

Sex-dependent effects of the uncompetitive N-methyl-D-aspartate receptor antagonist REL-1017 in G93A-SOD1 amyotrophic lateral sclerosis mice

Colognesi M, Shkodra A, Gabbia D, Kawamata H, Manfredi P, Manfredi G, De Martin S

Front Neurol. 2024 May 3:15:1384829.

DOI: 10.3389/fneur.2024.1384829

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 Oct;273(7):1463-1476.

DOI: 10.1007/s00406-023-01571-4

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

J Clin Psychopharmacol. 2022 Sep-Oct;42(5):503-506.

DOI: 10.1097/JCP.0000000000001583

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

Front Pharmacol. 2021 Apr 28:12:671859.

DOI: 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

J Clin Psychopharmacol. 2019 May/Jun;39(3):226-237.

DOI: 10.1097/jcp.0000000000001035

Published articles

Drug–drug interaction studies of esmethadone (REL‐1017) involving CYP3A4‐ and CYP2D6‐mediated metabolism

Ferri N, De Martin S, Stuart J, Traversa S, Folli F, Pappagallo M, O’Gorman C, Guidetti C, Mattarei A, Inturrisi C, Manfredi P

Drugs R D. 2024 Mar;24(1):51-68.

DOI: 10.1007/s40268-023-00450-6

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 (Basel). 2022 Aug 13;15(8):997.

DOI: 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 (Basel). 2022 Jul 17;15(7):882.

DOI: 10.3390/ph15070882

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

Sci Rep. 2022 Jul 6;12(1):11389.

DOI: 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

Front Pharmacol. 2022 Apr 25:13:863959.

DOI: 10.3389/fphar.2022.863959

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.

DOI: 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 Dec;44(13):2230-2238.

DOI: 10.1038/s41386-019-0501-x

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, Manfredi P

Int J Mol Sci. 2022 Oct 13;23(20):12196.

DOI: 10.3390/ijms232012196

Published articles

Letter to the Editor regarding ‘Unique pharmacodynamic properties and low abuse liability of the µ-opioid receptor ligand (S)-methadone’

Pappagallo M, Kosten T, Gorodetzky C, Vocci F, Sapienza F, De Martin S, Comai S, Mattarei A, Inturrisi C, Manfredi P

Mol Psychiatry. 2024 May 28.

DOI: 10.1038/s41380-024-02621-6

Published articles

Effect of time from onset of major depressive disorder on the therapeutic response to esmethadone (REL-1017)

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

J Clin Psychiatry 2024;85(2):22m14735

DOI: 10.4088/JCP.22m14735

Published articles

N-methyl-D-aspartate receptors and depression: linking psychopharmacology, pathology and physiology in a unifying hypothesis for the epigenetic code of neural plasticity

Comai S, De Martin S, Mattarei A, Guidetti C, Pappagallo M, Folli F, Alimonti A, Manfredi P

Pharmaceuticals 2024, 17(12), 1618

DOI: 10.3390/ph17121618

Congress presentations

Semaglutide and psilocybin in a mouse model of obesity, steatotic liver disease and type 2 diabetes

De Martin S

Obesity Week 2024

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Congress presentations

N-Methyl-D-Aspartate receptor uncompetitive antagonists and depression, from psychopharmacology and pathology to physiology: a unifying hypothesis for the epigenetic code of neural plasticity

Comai S, De Martin S, Mattarei A, Guidetti C, Folli F, Alimonti A, Pappagallo M, Manfredi P

American Society of Clinical Psychopharmacology (ASCP) 2024

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Congress presentations

Esmethadone (REL-1017) improves cognition in patients with severe major depressive disorder and inadequate response to standard antidepressants: a post hoc analysis from a Phase 3 randomized controlled trial

Guidetti C, De Martin S, Papakostas G, Pani L, Apicella M, Hernandez Ortiz J, Pappagallo M, Manfredi P, Fava M

American College of Neuropsychopharmacology (ACNP) 2024

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Congress presentations

Depression severity and efficacy outcomes: post hoc analyses from a Phase 3 trial of the novel NMDAR antagonist antidepressant candidate esmethadone for the adjunctive treatment for MDD with inadequate response to standard antidepressants

Fava M, Pani L, De Martin S, Kröger C, Champasa P, Guidetti C, Comai S, Mattarei A, Folli F, Traversa S, Gorodetzky C, Vocci F, Sapienza F, Kosten T, Inturrisi C, Bushnell D, Kappler M, Manfredi P, Pappagallo M

American College of Neuropsychopharmacology (ACNP) 2024

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Congress presentations

Chronic non-psychedelic psilocybin therapy promotes visual rehabilitation in mice post-occipital stroke

Nasini S, Barzon B, Cambiaghi M, De Martin S, Mattarei A, Pappagallo M, Manfredi P, Comai S

Society for Neuroscience (SfN) 2024

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Congress presentations

Long-term safety and efficacy of esmethadone in patients with major depressive disorder: findings from a 12-Month open-label study

Fava M, Pani L, De Martin A, Cutler A, Kröger C, Champasa P, Guidetti C, Comai S, Mattarei A, Folli F, Bushnell D, Traversa S, Inturrisi C, Manfredi P, Pappagallo M

American Society of Clinical Psychopharmacology (ASCP) 2024

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Congress presentations

No indication of abuse or withdrawal potential with esmethadone (REL-1017): results from two Phase 3 randomized placebo-controlled trials in patients with major depressive disorder

Shram M, Pappagallo 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 C, Manfredi P

American College of Neuropsychopharmacology (ACNP) 2023

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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 placebo-controlled trial

Fava M, Stahl S, Pani L, De Martin S, O’Gorman C, Guidetti C, Gorodetzky C, Vocci F, Sapienza F, Kosten T, Alimonti A, Comai S, Mattarei A, Folli F, Bushnell D, Kroeger C, Champasa P, Traversa S, Inturrisi CE, Manfredi P, Pappagallo M

American College of Neuropsychopharmacology (ACNP) 2023

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Congress presentations

The serotonin receptor agonist psilocybin as a novel therapeutic approach for NAFLD: preclinical studies

De Martin S, Gabbia D, Colognesi M, Zanotto I, Sayaf K, Comai S, Mattarei A, Banzato M, Folli F, Centofanti L, Traversa S, Pappagallo M, Manfredi P

American Association For The Study Of Liver Diseases (AASLD) 2023

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Congress presentations

Behavioral effects of a 14-day repeated treatment with psilocybin at a low non-psychedelic dose: a preliminary study in C57BL/6J mice

Nasini S, Colognesi M, Tidei S, De Martin S, Banzato M, Mattarei A, Folli F, Pappagallo M, Manfredi P, Comai S

European College of Neuropsychopharmacology (ECNP) 2023

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Congress presentations

Efficacy of esmethadone (REL-1017) in patients with major depressive disorder and antidepressant tolerance (antidepressant tachyphylaxis)

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

European College of Neuropsychopharmacology (ECNP) 2023

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Congress presentations

No indication of abuse potential and absence of withdrawal from esmethadone (REL-1017) in patients with major depressive disorder

Shram M, Pappagallo 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 C, Manfredi P

European College of Neuropsychopharmacology (ECNP) 2023

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

American Society of Clinical Psychopharmacology (ASCP) 2023

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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 P, Pappagallo M

American Society of Clinical Psychopharmacology (ASCP) 2023

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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

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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

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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

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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

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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 C, Manfredi P, Pappagallo M

The College of Problems of Drug Dependence (CPDD) 2022

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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

American Society of Clinical Psychopharmacology (ASCP) 2022

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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) 2022

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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) 2021

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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) 2021

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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) 2021

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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

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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

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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 M, Traversa S, Manfredi P

Neuroscience Education Institute (NEI) 2021

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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) 2021

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