amitifadine (EB-1010) / Ethismos Research - LARVOL DELTA

Ansofaxine hydrochloride inhibits tumor growth and enhances Anti-TNFR2 in murine colon cancer model. (PubMed, Front Pharmacol) - " We treated CT26, HCT116, MCA38 and SW620 colon cancer cells with fluoxetine (0-50 µM), ansofaxine hydrochloride (0-50 µM) and amitifadine hydrochloride (0-150 µM) to examine their effects on cell proliferation and apoptosis. In summary, our data reveal the role of ansofaxine hydrochloride in modulating the anti-tumor immunity. Our results support that exhausted CD8T is an important potential mechanism by which ansofaxine hydrochloride activates anti-tumor immunity and enhances anti-tumor effects of anti-TNFR2."

Journal • Preclinical • CNS Disorders • Colon Cancer • Colorectal Cancer • Depression • Gastrointestinal Cancer • Oncology • Psychiatry • Solid Tumor • Transplantation • CD4 • CD8 • TNFRSF1B

Modular Synthesis of Cyclopropane-Fused N-Heterocycles Enabled by Underexplored Diazo Reagents. (PubMed, Angew Chem Int Ed Engl) - "The operationally simple transformation, which proceeds through successive acylation, (3+2) cycloaddition and fragmentation, tolerates a broad range of functional groups and yields a wide spectrum of complex molecular scaffolds, including fused, bridged and spiro ring systems. We demonstrate the utility of this transformation in the concise syntheses of therapeutic agents milnaciprane and amitifadine."

Journal

Modular synthesis of lactam-fused cyclopropanes enabled by underexplored diazo reagents (ACS-Sp 2022) - "Application of the operationally simple method is demonstrated in the efficient synthesis of milnacipran and amitifadine, therapeutic agents that are used in the clinical treatment of fibromyalgia and alcoholism, respectively. Altogether, the broad substrate scope and modularity of the reported method promise wide-spread application and studies on its use in the synthesis of structurally unprecedented DNA-encoded libraries are currently ongoing."

Fibromyalgia • Musculoskeletal Pain • Pain • Rheumatology

Amitifadine, a triple reuptake inhibitor, reduces self-administration of the opiate remifentanil in rats. (PubMed, Psychopharmacology (Berl)) - "These studies show the promise of amitifadine as a treatment for countering opiate self-administration for adjunctive use with opioids for analgesia. Further studies are needed to determine the possible efficacy of amitifadine for combating opiate addiction or preventing it in humans during adjunctive use with opioids for chronic pain."

Journal • Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Pain • Substance Abuse

Prolonging the Reduction of Nicotine Self-Administration in Rats by Coadministering Chronic Nicotine With Amitifadine, a Triple Monoamine Reuptake Inhibitor With CYP2B6 Inhibitory Actions. (PubMed, Nicotine Tob Res) - "This study replicated the effects that chronic nicotine or chronic amitifadine, a triple reuptake inhibitor, significantly reduces nicotine self-administration in rats. It extends those findings by showing that the combination of chronic nicotine plus amitifadine causes significantly greater reduction in nicotine self-administration than either drug treatment alone. The combination of chronic amitifadine and chronic nicotine also causes a persistent significant reduction in nicotine self-administration after the end of treatment. The amitifadine and nicotine treatment should be assessed in humans to determine whether this combination provides greater efficacy in smoking cessation than transdermal nicotine treatment alone."

Journal • Preclinical • Tobacco Addiction • Tobacco Cessation

A Paroxetine- and Placebo-Controlled Study of 50 mg/Day and 100 mg/Day of EB-1010 Among Outpatients With Major Depressive Disorder Who Have Responded Inadequately to Prior Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin Norepinephrine Reupta (clinicaltrials.gov) - P2/3; N=342; Completed; Sponsor: Euthymics BioScience, Inc.; Active, not recruiting -> Completed

Trial completion • Biosimilar

Ethismos Research initiates $50 MM private placement led by venture.co brokerage services (P T) - "Ethismos Research, developing pharmaceutical treatments for chronic pain management, severe depression...announced the initiation of a $50 million private placement, led by managing broker-dealer, VENTURE.co Brokerage Services....Ethismos will use the proceeds to fund a Phase 2 clinical trial program for its lead candidate, amitifadine….will also be assessed in a second Phase 2 program in either maintenance of depression remission after ketamine treatment....Amitifadine has undergone initial FDA safety and dosing trials and is ready to move into Phase 2 (efficacy) trials."

Financing • New P2 trial

Acute and chronic amitifadine, a triple monoaminergic re-uptake inhibitor reduces self-administration of both nicotine and the opiate remifentanil (Neuroscience 2019) - "These studies show the promise of amitifadine as a treatment for countering opiate self-administration. Further studies are needed to determine the possible efficacy of amitifadine for combating opiate addiction in people."

Pharmacological interventions targeting anhedonia in patients with major depressive disorder: A systematic review. (PubMed, Prog Neuropsychopharmacol Biol Psychiatry) - "Among the identified studies, the efficacy of 14 different pharmacotherapies on measures of anhedonia were evaluated, including melatonergic agents (i.e. agomelatine), monoaminergic agents (i.e. moclobemide, clomipramine, bupropion, venlafaxine, fluoxetine, amitifadine and levomilnacipran, escitalopram, and sertraline), glutamatergic agents (i.e., ketamine and riluzole), stimulants (i.e., methylphenidate), and psychedelics (i.e., psilocybin). Continued research is warranted to further support the efficacy of mechanistically-distinct antidepressants in treating symptoms of anhedonia in MDD. Future research should also aim to parse out the heterogeneous effects of different pharmacotherapies on anhedonic symptoms."

Clinical • Journal • Review