NP 10679 / Neurop - LARVOL DELTA

New advances in small molecule drugs targeting NMDA receptors. (PubMed, Acta Pharmacol Sin) - "Among various therapeutic indications, depression has emerged as an especially active area of investigation, with mechanistically diverse compounds ranging from broad-spectrum channel blockers (ketamine, dextromethorphan, esmethadone) to glycine site modulators (rapastinel, 4-chlorokynurenine, D-cycloserine) and allosteric modulators (apimostinel, zelquistinel), progressing through clinical pipelines. Beyond depression, NMDA receptor-targeted drug discovery is also advancing in other challenging CNS disorders, including neurodegenerative diseases (salzanemdor, NYX-458), pain (NYX-2925), epilepsy (radiprodil), and stroke (nelonemdaz, NP10679). Collectively, these developments reflect the maturation of NMDA receptor pharmacology and reaffirm the broad therapeutic potential of NMDA receptor modulation, while highlighting promising directions for future drug discovery."

Journal • Review • Cardiovascular • CNS Disorders • Depression • Epilepsy • Mental Retardation • Pain • Psychiatry

NP10679: A new horizon for neuroprotection in aneurysmal subarachnoid hemorrhage. (PubMed, J Pharmacol Exp Ther) - No abstract available

Journal • Cardiovascular • Hematological Disorders • Subarachnoid Hemorrhage

Clinical development of the GluN2B-selective NMDA receptor inhibitor NP10679 for the treatment of neurologic deficit after subarachnoid hemorrhage. (PubMed, J Pharmacol Exp Ther) - "SIGNIFICANCE STATEMENT: This report describes the properties and utility of the GluN2B-selective pH-sensitive N-methyl-d-aspartate receptor inhibitor, NP10679, in a well characterized rodent model of subarachnoid hemorrhage. We show that the administration of NP10679 improves long-term neurological function following subarachnoid hemorrhage and that in rats, there are no drug-drug interactions between NP10679 and nimodipine, the standard of care for this indication."

Journal • Cardiovascular • Hematological Disorders • Ischemic stroke • Subarachnoid Hemorrhage • GRIN2B

Clinical Development of the GluN2B-selective NMDA Receptor Inhibitor NP10679 for the Treatment of Neurologic Deficit after Subarachnoid Hemorrhage. (PubMed, J Pharmacol Exp Ther) - "Significance Statement This report describes the properties and utility of the GluN2B-selective pH-sensitive NMDA receptor inhibitor, NP10679, in a well-characterized rodent model of subarachnoid hemorrhage. We show that the administration of NP10679 improves long-term neurological function following subarachnoid hemorrhage, and that in rats there are no drug-drug interactions between NP10679 and nimodipine, the standard of care for this indication."

Journal • Cardiovascular • Hematological Disorders • Ischemic stroke • Subarachnoid Hemorrhage • GRIN2B

Phase 1 Clinical Results for NP10679, a pH-sensitive GluN2B-selective N-methyl-d-aspartate Receptor Inhibitor. (PubMed, Clin Pharmacol Drug Dev) - P1 | "The only notable side effect in this clinical trial was modest somnolence at higher doses, atypical in that the subject could easily be aroused. The overall results suggest that NP10679 is a candidate for further development for use in acute brain injury, such as ischemic stroke or aneurysmal subarachnoid hemorrhage, as well as for use in neuropsychiatric indications."

Journal • P1 data • Cardiovascular • CNS Disorders • Hematological Disorders • Ischemic stroke • Psychiatry • Subarachnoid Hemorrhage • Vascular Neurology

A GluN2B-selective inhibitor of NMDA receptor function with enhanced potency at acidic pH and oral bioavailability for clinical use. (PubMed, J Pharmacol Exp Ther) - "The clinical candidate molecule, NP10679, has high oral bioavailability with good brain penetration, and is suitable for both intravenous and oral dosing for therapeutic use in man. Significance Statement This study identifies a new series of GluN2B-selective negative allosteric modulators with properties appropriate for clinical advancement. The compounds are more potent at acidic pH associated with ischemic tissue, and this property should increase the therapeutic safety of this class by improving efficacy in affected tissue while sparing NMDA receptor block in healthy brain."

Clinical • Journal

A Multiple Ascending Dose Study of Safety and Pharmacokinetics of NP10679 in Normal Healthy Volunteers (clinicaltrials.gov) - P1; N=24; Completed; Sponsor: Neurop Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion