Esmethadone (REL-1017) and Other Uncompetitive NMDAR Channel Blockers May Improve Mood Disorders via Modulation of Synaptic Kinase-Mediated Signaling.

This article presents a mechanism of action hypothesis to explain the rapid antidepressant effects of esmethadone (REL-1017) and other uncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonists and presents a corresponding mechanism of disease hypothesis for major depressive disorder (MDD). Esmethadone and other uncompetitive NMDAR antagonists may restore physiological neural plasticity in animal models of depressive-like behavior and in patients with MDD via preferential tonic block of pathologically hyperactive GluN2D subtypes. Tonic Ca currents via GluN2D subtypes regulate the homeostatic availability of synaptic proteins.

The Genomic Architecture of Pregnancy-Associated Plasticity in the Maternal Mouse Hippocampus.

Pregnancy is associated with extraordinary plasticity in the maternal brain. Studies in humans and other mammals suggest extensive structural and functional remodeling of the female brain during and after pregnancy. However, we understand remarkably little about the molecular underpinnings of this natural phenomenon.

Variations in age structure and growth in congeners Lacerta viridis and Lacerta media.

Determining the age of any species allows it to be analyzed from the ontogenetic, demographic, and ecological perspectives. In the present study, we tested the hypothesis that the age structure of congener species (Lacerta media and Lacerta viridis) with the same ecological niche may vary in different areas. In this context, we applied skeletochronology method to reveal various demographic parameters, such as age structure, longevity, age at sexual maturity, growth rate, survival rate, adult life expectancy, and the relationship between age and body size in the green lizard, L.

REL-1017 (Esmethadone) as Adjunctive Treatment in Patients With Major Depressive Disorder: A Phase 2a Randomized Double-Blind Trial.

The purpose of this study was to examine the effects of REL-1017 (esmethadone), a novel -methyl-d-aspartate receptor (NMDAR) channel blocker, in patients with major depressive disorder who failed to benefit from one to three standard antidepressant treatments in their current major depressive episode. A 7-day phase 2 multicenter randomized double-blind placebo-controlled trial, comprising three arms, was conducted to assess the safety, tolerability, pharmacokinetics, and efficacy of two dosages of REL-1017 (25 mg or 50 mg orally once a day). Patients were randomly assigned in a 1:1:1 ratio to placebo (N=22), REL-1017 25 mg/day (N=19), or REL-1017 50 mg/day (N=21).