usmarapride (SUVN-D4010) / Suven Life Sci - LARVOL DELTA

Usmarapride (SUVN-D4010), a 5-HT receptor partial agonist for the potential treatment of Alzheimer's disease: Behavioural, neurochemical and pharmacological profiling. (PubMed, Eur J Pharmacol) - "donepezil, rivastigmine, galantamine, memantine etc. either alone or in combination show modest efficacy without changing the course of the disease...Aducanumab, a monoclonal antibody is a disease modifying therapeutic agent targeting the toxic amyloid beta (Aβ) proteins for its clearance...Usmarapride also potentiated the pharmacological effects of donepezil in animal models. To conclude, usmarapride may be a promising intervention for alleviating the cognitive dysfunction in AD patients with disease modifying potential."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • APP

Usmarapride Oxalate (SUVN-D4010): A Serotonin-4 Receptor Partial Agonist for the Treatment of Cognitive Disorders (AAIC 2022) - No abstract available

CNS Disorders • Cognitive Disorders • Developmental Disorders

A selective and accurate liquid chromatography-tandem mass spectrometry method for the quantitation of the novel 5-HT receptor partial agonist SUVN-D4010 (Usmarapride) in human plasma and urine. (PubMed, J Pharm Biomed Anal) - "SUVN-D4010 was found to be stable in human plasma and urine at the defined storage conditions. The validated method was successfully applied to quantitate SUVN-D4010 in human plasma and urine from a clinical first-in-human study conducted to evaluate its safety, tolerability, and pharmacokinetics in healthy adults."

Journal • Alzheimer's Disease • CNS Disorders

SUVN-D4010: A serotonin-4 receptor partial agonist for the treatment of cognitive disorders. (PubMed, Alzheimers Dement) - "SUVN-D4010 is a potent, selective, orally bioavailable and brain penetrant 5-HT receptor partial agonist with potential utility in treatment of cognitive disorders."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders

Usmarapride (SUVN-D4010): A 5-HT 4 receptor partial agonist alleviates haloperidol-induced Parkinson’s disease associated cognitive dysfunction (Neuroscience 2021) - "Haloperidol is a classical antipsychotic drug known for its propensity to cause extrapyramidal symptoms and cognitive impairment, due to the blockade of striatal dopamine D 2 receptors. Significant increase in novel juvenile social investigation time or discriminative index was observed for the groups treated with usmarapride or rivastigmine, relative to familiar juvenile or vehicle control group, respectively. Usmarapride ameliorated PD related dementia in an animal model, thus it could be a future promising therapeutic strategy for PD associated dementia, thereby to improve the patients' hQOL."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Parkinson's Disease

[VIRTUAL] SUVN-D4010: A serotonin-4 receptor partial agonist for the treatment of cognitive disorders (AAIC 2021) - "SUVN-D4010 significantly increased extracellular acetylcholine levels as a standalone, or treatment adjunct to donepezil. SUVN-D4010 is a potent, selective, orally bioavailable and brain penetrant 5-HT 4 receptor partial agonist with potential utility in treatment of cognitive disorders."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders

Discovery and Preclinical Characterization of Usmarapride (SUVN-D4010): A Potent, Selective 5-HT Receptor Partial Agonist for the Treatment of Cognitive Deficits Associated with Alzheimer's Disease. (PubMed, J Med Chem) - "Phase 1 clinical studies have been completed and projected efficacious concentration was achieved without any major safety concerns. Phase 2 enabling long-term safety studies have been completed with no concerns for further development."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • APP

First-in-Human Studies to Evaluate the Safety, Tolerability, and Pharmacokinetics of a Novel 5-HT Partial Agonist, SUVN-D4010, in Healthy Adult and Elderly Subjects. (PubMed, Clin Drug Investig) - P1 | "SUVN-D4010 was found to be safe and well tolerated in healthy human subjects. SUVN-D4010 followed linear pharmacokinetics across the dose range. Accumulation was in the range of 1.3- to 1.4-fold after multiple dosing. Renal excretion is not the major route of elimination. Food had no effect on the exposures but increased the t of SUVN-D4010. Exposures were lower in females and elderly subjects suggesting sex and age effects on the pharmacokinetics of SUVN-D4010 and possible dose adjustment in these populations. SUVN-D4010 was well tolerated and safe in elderly subjects after a single dose. Clinical trial identifiers: NCT02575482 and NCT03031574."

Clinical • Journal • P1 data • PK/PD data • CNS Disorders • Cognitive Disorders • Developmental Disorders • Pain

SUVN-D4010, a 5-HT4 receptor partial agonist with antidepressant properties: Behavioral and neurochemical studies in mice and rats (Neuroscience 2019) - "Additionally, SUVN-D4010 in combination with serotonin re-uptake inhibitor (SSRI) paroxetine produced synergistic effects on serotonin levels in ventral hippocampus of Wistar rats. Results from these preclinical studies provide strong evidence for SUVN-D4010 in alleviating depressive symptoms by complementary mechanism with existing anti-depressants."

Preclinical