TS-161 / Taisho - LARVOL DELTA

Antidepressant Effects of TS-161 in Treatment-Resistant Depression (clinicaltrials.gov) - P2 | N=5 | Completed | Sponsor: National Institute of Mental Health (NIMH) | Recruiting ➔ Completed | N=25 ➔ 5 | Trial completion date: Jun 2025 ➔ May 2024 | Trial primary completion date: Jun 2025 ➔ May 2024

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Antidepressant Effects of TS-161 in Treatment-Resistant Depression (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: National Institute of Mental Health (NIMH) | Trial completion date: Jun 2024 ➔ Jun 2025 | Trial primary completion date: Jun 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Antidepressant Effects of TS-161 in Treatment-Resistant Depression (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: National Institute of Mental Health (NIMH) | Trial completion date: Jun 2023 ➔ Jun 2024 | Trial primary completion date: Jun 2023 ➔ Jun 2024

Trial completion date • Trial primary completion date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

mGlu2/3 receptor antagonists for depression: overview of underlying mechanisms and clinical development. (PubMed, Eur Arch Psychiatry Clin Neurosci) - "Triggered by the ground-breaking finding that ketamine exerts robust and rapid-acting antidepressant effects in patients with treatment-resistant depression, glutamatergic systems have attracted attention as targets for the development of novel antidepressants. Despite some discouraging results for an mGlu2/3 receptor antagonist decoglurant (classified as a negative allosteric modulator [NAM]) in patients with major depressive disorder, clinical trials of two mGlu2/3 receptor antagonists, a phase 2 trial of TS-161 (an orthosteric antagonist) and a phase 1 trial of DSP-3456 (a NAM), are presently on-going. mGlu2/3 receptors still hold promise for the development of safer and more efficacious antidepressants."

Journal • Review • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Clinical investigations of compounds targeting metabotropic glutamate receptors. (PubMed, Pharmacol Biochem Behav) - "PET ligands for mGlu5Rs have been studied in a range of patient populations and several mGlu5R antagonists have been tested for potential efficacy in patients including mavoglurant, diploglurant, basimglurant, GET 73, and ADX10059...Fenobam was approved for use as an anxiolytic prior to its recognition as an mGlu5R antagonist. mGlu2/3R agonists (pomaglumated methionil) and mGlu2R agonists (JNJ-40411813, AZD 8529, and LY2979165) have been studied in patients with schizophrenia with promising but mixed results. Antagonists of mGlu2/3Rs (decoglurant and TS-161) have been studied in depression where TS-161 has advanced into a planned Phase 2 study in treatment-resistant depression...The mGlu4R potentiator, foliglurax, did not meet its primary endpoint in patients with Parkinson's disease. Ongoing efforts to develop mGluR-targeted compounds continue to promise these glutamate modulators as medicines for psychiatric and neurological disorders."

Journal • CNS Disorders • Depression • Developmental Disorders • Epilepsy • Fragile X Syndrome • Gastroenterology • Gastroesophageal Reflux Disease • Genetic Disorders • Mental Retardation • Mood Disorders • Movement Disorders • Pain • Parkinson's Disease • Psychiatry • Schizophrenia

Evaluation of the safety, tolerability and pharmacokinetic profiles of TP0473292 (TS-161), a prodrug of a novel orthosteric mGlu2/3 receptor antagonist TP0178894, in healthy subjects and its antidepressant-like effects in rodents. (PubMed, Int J Neuropsychopharmacol) - "The mGlu2/3 receptor antagonist prodrug TP0473292 is safe and well-tolerated, is orally bioavailable in humans with extensive conversion into the active metabolite TP0178894 with sufficient CSF penetration to exert the anticipated pharmacological effects, and is a promising candidate for further clinical development in treatment of patients with depression."

Clinical • Journal • PK/PD data • Preclinical • CNS Disorders • Depression • Psychiatry

Novel Glutamatergic Modulators for the Treatment of Mood Disorders: Current Status. (PubMed, CNS Drugs) - "This manuscript gives a brief overview of the glutamate system and its relevance to rapid antidepressant response and discusses the existing clinical evidence for glutamate receptor-modulating agents, including (1) broad glutamatergic modulators ((R,S)-ketamine, esketamine, (R)-ketamine, (2R,6R)-hydroxynorketamine [HNK], dextromethorphan, Nuedexta [a combination of dextromethorphan and quinidine], deudextromethorphan [AVP-786], axsome [AXS-05], dextromethadone [REL-1017], nitrous oxide, AZD6765, CLE100, AGN-241751); (2) glycine site modulators (D-cycloserine [DCS], NRX-101, rapastinel [GLYX-13], apimostinel [NRX-1074], sarcosine, 4-chlorokynurenine [4-Cl-KYN/AV-101]); (3) subunit (NR2B)-specific N-methyl-D-aspartate (NMDA) receptor antagonists (eliprodil [EVT-101], traxoprodil [CP-101,606], rislenemdaz [MK-0657/CERC-301]); (4) metabotropic glutamate receptor (mGluR) modulators (basimglurant, AZD2066, RG1578, TS-161); and (5) mammalian target of rapamycin complex 1..."

Journal • Review • Bipolar Disorder • CNS Disorders • Depression • Gastrointestinal Disorder • Major Depressive Disorder • Mood Disorders • Psychiatry

Antidepressant Effects of TS-161 in Treatment-Resistant Depression (clinicaltrials.gov) - P2; N=25; Recruiting; Sponsor: National Institute of Mental Health (NIMH)

New P2 trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

First-in-Human Study With Single and Multiple Doses of TS-161 in Healthy Participants (clinicaltrials.gov) - P1; N=70; Completed; Sponsor: Taisho Pharmaceutical R&D Inc.; Recruiting ➔ Completed

Clinical • Trial completion

First-in-Human Study With Single and Multiple Doses of TS-161 in Healthy Participants (clinicaltrials.gov) - P1; N=70; Recruiting; Sponsor: Taisho Pharmaceutical R&D Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open