raseglurant (ADX-10059) / Addex - LARVOL DELTA

An updated patent review of mGlu5 negative allosteric modulators (2018 - present). (PubMed, Neuroscience) - "However, the clinical development of mGlu5 negative allosteric modulators (NAMs) has been limited by translational challenges, inconsistent efficacy, and safety concerns, particularly hepatotoxicity associated with early acetylene-containing scaffolds such as ADX10059...Recent patent-linked compounds such as TMP-301/HTL0014242, VU0424238, VU6031545, VU6024945, and AE90015 are presented alongside unconventional approaches, including GET-73, LCGM-10, antibodies, and nanobodies. It also covers clinical progress, including the repurposing of mavoglurant/STP7 for cocaine use disorder. Overall, the field aims for safer, more selective, and better-controlled mGlu5 modulation strategies, but challenges related to efficacy, tolerability, and patient selection continue to hinder clinical success."

Journal • Review • CNS Disorders • Depression • Fragile X Syndrome • Genetic Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

Targeted Inhibition of mGlu5 Receptors in the Contralesional Hemisphere Improves Functional Recovery After Stroke. (PubMed, Stroke) - "JF-NP-26 is a caged derivative of the mGlu5 receptor NAM, raseglurant, inactive on its own, and can be activated by visible light of 405 nm...These findings demonstrate that the homotopic contralateral somatosensory cortex is a key site of action of systemic mGlu5 receptor NAMs in enhancing restorative processes important for recovery after stroke. Targeted, light-modulated drugs represent a potential future therapeutic strategy to enhance recovery of function after stroke."

Journal • Cardiovascular • Ischemic stroke

Drn'S vglut3+tph2+ neurons projecting to cea play a critical role in relapse after food-based voluntary abstinence from methamphetamine (Neuroscience 2025) - "The effect of DRN reversible inactivation was tested by NAM of mGluR5 via JF-NP-26, which releases raseglurant under 405 nm light delivered through an optical fiber implanted in the DRN. Our results suggest that the VGLUT3+/TPH2+ output from the DRN to the CeA is critical to the incubation of METH craving after voluntary abstinence."

CNS Disorders • Psychiatry

Design and validation of a low-cost photomodulator for in vivo photoactivation of a mGluR5 inhibitor. (PubMed, Biomed Eng Lett) - "They demonstrate the in vivo capabilities of the photomodulator by photoreleasing raseglurant, an mGluR5 inhibitor, to treat pain in an acute rat model and follow this study by showing how to reconfigure the photomodulator to work wirelessly and interface with other biomedical devices. The online version contains supplementary material available at 10.1007/s13534-023-00334-3."

Journal • Preclinical • Pain

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

The mGlu Receptor Protomer-Mediated Dopamine D Receptor Trans-Inhibition Is Dependent on the Adenosine A Receptor Protomer: Implications for Parkinson's Disease. (PubMed, Mol Neurobiol) - "In agreement, the mGluR-negative allosteric modulator raseglurant significantly reduced the haloperidol-induced catalepsy in mice, and in AR knockout mice, the haloperidol action had almost disappeared, supporting a functional role for mGluR and AR in enhancing DR blockade resulting in catalepsy. The results represent a relevant example of integrative activity within higher-order heteroreceptor complexes."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease