fluoroethylnormemantine (RST-101) / ReST Therap - LARVOL DELTA

ReST Therapeutics Announces U.S. FDA Acceptance of Investigational New Drug (IND) Application for RST-101 for the Early Treatment of Post-Traumatic Stress Disorder (PTSD) (Businesswire) - "The IND acceptance clears the way for ReST Therapeutics to initiate a first-in-human clinical trial evaluating RST-101 in healthy volunteers."

First-in-human • IND • Post-traumatic Stress Disorder

Mu Opioid Receptor Activation is Required for NMDA Receptor Antagonist Effects on Stress-induced Maladaptive Behavior. (PubMed, Biol Psychiatry) - "MOR activation is required for the efficacy of both (R,S)-ketamine and FENM against stress-induced maladaptive behavior, suggesting that these compounds function through an indirect effect of NMDAR antagonism on endogenous opioid signaling."

Journal • CNS Disorders • Depression • Pain • Psychiatry • CA3

Long-Term Treatment with Fluoroethylnormemantine (FENM) Alleviated Memory Deficits, Amyloid Pathology, and Microglial Reaction in APP/PS1 Mice. (PubMed, ACS Pharmacol Transl Sci) - "Fluoroethylnormemantine (FENM, RST-01) shows different pharmacological properties from Memantine. FENM confirmed, under a chronic presymptomatic treatment, its neuroprotective efficacy in AD. Our data particularly suggested that an impact on Aβ and microglia could be related to the preservation of cognitive functions."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Inflammation

First-In-Human (FIH), Single Ascending Dose (SAD) Study of FluoroEthylNorMemantine (FENM) (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: ReST Therapeutics | N=36 ➔ 0 | Trial completion date: Sep 2024 ➔ May 2024 | Initiation date: Sep 2023 ➔ May 2024 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Sep 2024 ➔ May 2024

Enrollment change • Trial completion date • Trial initiation date • Trial primary completion date • Trial withdrawal • Alzheimer's Disease • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry

Targeting N-Methyl-d-Aspartate Receptors in Neurodegenerative Diseases. (PubMed, Int J Mol Sci) - "The pharmacology of different NMDAR antagonists and their therapeutic potentialities will be presented. In particular, a focus will be given on fluoroethylnormemantine (FENM), an investigational drug with very promising development as a neuroprotective agent in Alzheimer's disease, in complement to its reported efficacy as a tomography radiotracer for NMDARs and an anxiolytic drug in post-traumatic stress disorder."

Journal • Review • Alzheimer's Disease • CNS Disorders • Huntington's Disease • Mood Disorders • Movement Disorders • Parkinson's Disease • Post-traumatic Stress Disorder • GRIN2A

Fluoroethylnormemantine (FENM) shows synergistic protection in combination with a sigma-1 receptor agonist in a mouse model of Alzheimer's disease. (PubMed, Neuropharmacology) - "Fluoroethylnormemantine (FENM) is a Memantine derivative with anti-amnesic and neuroprotective activities showed in the Aβ pharmacological mouse model of Alzheimer's disease (AD). Memantine led to synergistic combination in short-term memory but poorly in long-term memory responses, with either PRE-084 or Donepezil. These study showed that drug combinations based on FENM and S1R agonists may lead to highly effective and synergistic protection in AD, particularly on short-term memory."

Combination therapy • Journal • Preclinical • Alzheimer's Disease • CNS Disorders

Neuroprotective and mnesic-improving effects of Fluoroethylnormemantine (FENM) in the Aß25-35 mouse model of Alzheimer's disease (CTAD 2023) - "Background: Objectives: Fluoroethylnormemantine (FENM) is an analogue of Memantine originally synthesized as a precursor for PET imaging. We confirm in cognitive paradigm the previously published histopathological observations of a neuroprotective effect of FENM, which appears to be superior to Memantine. This efficacy is further increase with a continuous mode of administration via Alzet pump. Finally, whereas Memantine effects is transient, FENM’ efficacy is long lasting, non-vanishing and sustained even after treatment discontinuation strongly suggesting a disease modifying activity."

Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation

First-In-Human (FIH), Single Ascending Dose (SAD) Study of FluoroEthylNorMemantine (FENM) (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: ReST Therapeutics

New P1 trial • Alzheimer's Disease • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry