estianeptine (TNX-4300) / Tonix - LARVOL DELTA

Tianeptine: enantiomeric separations, structural assignment, and biological interactions. (PubMed, Talanta) - "The total tianeptine and its enantiomeric ratio in recreational products were analyzed by HPLC-UV after developing a robust extraction procedure with ethanol for liquid and solid products. The assessment of the enantioselective binding of tianeptine to many essential proteins revealed higher affinity of human serum albumin for the S-tianeptine."

Journal • Addiction (Opioid and Alcohol)

Tianeptine Exposures Reported to United States Poison Centers, 2015-2023. (PubMed, J Med Toxicol) - "This study demonstrates the toxicity and rapid increase of tianeptine exposures reported to US poison centers. Uniform regulation of tianeptine across all states may offer an important strategy to help mitigate this public health problem."

Journal • Critical care

Differential Effects of Enantiomers (S)- And (R)-Tianeptine on Neurite Outgrowth and Mitochondrial Activity in Cultured Glutamatergic Neurons (ACNP 2023) - "Comparison of (S)- and (R)-tianeptine treatment of iCell Glutaneurons revealed significant differences in their effects on neurite outgrowth metrics and measures of mitochondrial function. (S)-tianeptine significantly increases neurite growth and synaptic connectivity in this in vitro neuronal system. (S)-tianeptine also increases mitochondrial staining in neurites, which may reflect increased activity or transport of mitochondria into growing neurites."

CNS Disorders • Depression • Psychiatry

The Enantiomer (R)-Tianeptine, but not (S)-Tianeptine, is an Agonist on the µ-Opioid Receptor and Decreases Immobility in the Murine Forced Swim Test (ACNP 2023) - "Racemic tianeptine and sertraline served as positive controls. (S)-tianeptine was devoid of MOR agonist activity, whereas (R)-tianeptine showed MOR agonism similar to that observed with racemic tianeptine. In the FST experiments, (S)-tianeptine did not reduce immobility at any dose tested, whereas (R)-tianeptine significantly reduced immobility at the higher doses (10 and 30 mg/kg). These findings suggest that (R)-tianeptine (or its main metabolite, an isomer of MC5), is responsible for the MOR-mediated effects of racemic tianeptine, including reduced immobility in the FST."

Preclinical • Alzheimer's Disease • Bipolar Disorder • CNS Disorders • Cognitive Disorders • Depression • Mood Disorders • Psychiatry

Tonix Pharmaceuticals Announces Presentation of Data Supporting Development of Racemic and Single (S)-Isomer Tianeptine, Plastogen Anti-Depressants, at the American Society of Clinical Psychopharmacology Meeting (GlobeNewswire) - "TNX-601 ER is being tested in a potentially pivotal Phase 2 trial for the treatment of major depressive disorder (MDD) for which results of a preplanned interim analysis are expected in the fourth quarter of 2023....The findings reported at the meeting show how the pharmacokinetics of oral TNX-601 ER in humans differ from intraperitoneal (i.p.) tianeptine in mice. In humans, after an oral dose of TNX-601 ER the half-life of tianeptine in the blood is approximately 5-7 hours. In contrast, in mice after an i.p. dose of tianeptine the half-life of tianeptine in the blood has been reported to be less than approximately 30 minutes and the behavioral effects appear dominated by the longer-lasting MC5 metabolite, which maintains µ-opioid receptor activity. The data Tonix presented also show that the (R)-isomer of tianeptine is responsible for the decrease in immobility in the mouse forced swim test after i.p. administration."

P2 data • Preclinical • Alzheimer's Disease • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Parkinson's Disease

Tonix Pharmaceuticals Announces Poster Presentation at the 2023 American Society of Clinical Psychopharmacology (ASCP) Annual Meeting (GlobeNewswire) - "Tonix Pharmaceuticals...today announced that Gregory Sullivan, M.D., Chief Medical Officer of Tonix Pharmaceuticals, will present a poster at the 2023 American Society of Clinical Psychopharmacology (ASCP) Annual Meeting being held May 30 – June 2, 2023, at the Loews Miami Beach Hotel in Miami Beach, Florida. The poster will provide an update on the status of the Phase 2 UPLIFT study of TNX-601 ER (tianeptine hemioxalate extended-release tablets) for the treatment of major depressive disorder (MDD). The poster will also highlight advances in the understanding of tianeptine’s mechanism of action and provide new details regarding the preclinical development of the (S)-isomer of tianeptine, TNX-4300 (estianeptine) for MDD, Alzheimer’s disease, and Parkinson’s disease."

P2 data • Preclinical • Alzheimer's Disease • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Parkinson's Disease

Tonix Pharmaceuticals Announces the Isolation and Characterization of the (S)-Isomer of Tianeptine, TNX-4300 (Estianeptine), Now Under Development for Psychiatric and Neurodegenerative Diseases (GlobeNewswire) - "Tonix Pharmaceuticals...today announced the isolation and functional characterization of the two mirror image isomers of racemic tianeptine, which is marketed outside the U.S. as a treatment for major depressive disorder (MDD). Tonix scientists discovered that the (S)-isomer of tianeptine activates PPAR-β/δ, restores neuroplasticity in neuronal tissue culture and is free of µ-opioid receptor activity. In contrast, (R)-tianeptine activates the µ-opioid receptor and lacks PPAR-β/δ activity. Based on these discoveries, Tonix has begun preclinical development of the (S)-isomer, TNX-4300 (estianeptine)*, as a treatment for MDD, bipolar disorder, Alzheimer’s disease, and Parkinson’s disease. Tonix is planning to submit data supporting tianeptine’s mechanism of action for presentation at upcoming scientific conferences and for publication in peer reviewed journals."

Preclinical • Alzheimer's Disease • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Parkinson's Disease • Post-traumatic Stress Disorder • Psychiatry • Tauopathies And Synucleinopathies