Psychopharmacology (Berl)
July 2022
Rationale: Ropanicant (SUVN-911) (3-(6-Chloropyridine-3-yloxymethyl)-2-azabicyclo (3.1.0) hexane hydrochloride) is a novel α4β2 nicotinic acetylcholine receptor (nAChR) antagonist being developed for the treatment of depressive disorders.
View Article and Find Full Text PDFJ Med Chem
August 2021
A series of oxadiazole derivatives were synthesized and evaluated as 5-hydroxytryptamine-4 receptor (5-HTR) partial agonists for the treatment of cognitive deficits associated with Alzheimer's disease. Starting from a reported 5-HTR antagonist, a systematic structure-activity relationship was conducted, which led to the discovery of potent and selective 5-HTR partial agonist 1-isopropyl-3-{5-[1-(3-methoxypropyl) piperidin-4-yl]-[1,3,4]oxadiazol-2-yl}-1H-indazole oxalate (Usmarapride, ). It showed balanced physicochemical-pharmacokinetic properties with robust nonclinical efficacy in cognition models.
View Article and Find Full Text PDFBackground: Central histamine H3 receptors are a family of presynaptic auto and heteroreceptors. Blockade of the presynaptic H3 receptors activates the downstream pathway(s) involved in the processes of learning and memory, making it a potential therapeutic option for ameliorating cognitive dysfunction. Samelisant (SUVN-G3031) is a potent and selective inverse agonist at the H3 receptors.
View Article and Find Full Text PDFResearch in Alzheimer's disease is going through a big turnaround. New palliative therapies are being reconsidered for the effective management of disease because of setbacks in the development of disease-modifying therapies. Serotonin 6 (5-HT6) receptor has long been pursued as a potential target for the symptomatic treatment of Alzheimer's disease.
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