Work

Update on the Development of SUVN‐I6107: A True Positive Allosteric Modulator of the Muscarinic M1 Acetylcholine Receptor for the Treatment of Dementia

Year: 2025

Type: article

Abstract: BACKGROUND: SUVN-I6107 is a novel and selective muscarinic M1 Positive Allosteric Modulator (PAM) being developed for the treatment of dementia due to neurodegenerative disorders. In the current research, the pharmacological properties of SUVN-I6107 in various animal models of cognitive deficits were investigated. METHODS: SUVN-I6107 was characterized using a calcium mobilization assay and the binding affinity towards the orthosteric M1 - M5 site was investigated to assess the selectivity. The effect of SUVN-I6107 on neuronal spike rate in coronal hippocampal slice electrophysiology was studied in agonist and PAM modes of testing. The pharmacokinetic properties of SUVN-I6107 were studied both in rodent and non-rodent species. The effect of SUVN-I6107 on MK-801 (antagonist of the NMDA receptor) induced memory deficits in rats using object recognition task (ORT) and delay-induced social memory deficits in rats using social recognition task (SRT) was studied. Furthermore, effects of SUVN-I6107 on neuronal markers like soluble amyloid precursor protein (sAPPα) and inositol 1 phosphate (IP-1) levels were studied in rats. RESULTS: of carbachol. SUVN-I6107 showed good oral bioavailability in rats, dogs, and monkeys. SUVN-I6107 was found to have brain penetration properties with adequate protein-free fraction. In a rat model, SUVN-I6107 has reversed the delay, scopolamine and MK-801 induced amnesias in ORT. SUVN-I6107 also significantly improved the memory in contextual fear conditioning task and SRT. Treatment with SUVN-I6107 produced significant increase in levels of cortical sAPPα and striatal IP-1 in rats. CONCLUSIONS: Results from the non-clinical studies suggest SUVN-I6107 may have memory enhancing property in various forms of dementias. SUVN-I6107 is currently being studied in a Phase-1 study (NCT06705088) to evaluate its safety, tolerability, pharmacokinetics, and pharmacodynamic effects after single and repeated administrations in healthy human subjects.

Source: Alzheimer s & Dementia

DOI: 10.1002/alz70856_099660