AF710B 10 mg – 60 capsules

AF710B 10 mg — 60 oral research capsules. AF710B (also referenced as ANAVEX 3-71) is a dual-target small molecule that acts as a positive allosteric modulator of the M1 muscarinic acetylcholine receptor and as an agonist at the sigma-1 receptor. Unlike direct muscarinic agonists, it potentiates M1 signalling only where endogenous acetylcholine is already present, which is the basis of the selectivity reported in the published preclinical literature. In animal models of amyloid pathology this dual profile has been characterised alongside markers of synaptic density and neuroinflammation [1,2].

Research Overview

AF710B is a spiro-indole small molecule developed as a dual M1 muscarinic / sigma-1 receptor ligand. The M1 receptor is a principal mediator of cholinergic signalling in the cortex and hippocampus, while the sigma-1 receptor is a chaperone protein at the mitochondria-associated endoplasmic reticulum membrane involved in cellular stress responses. Published preclinical work reports that the compound’s effects on amyloid pathology, synaptic markers and cognitive performance in transgenic rodent models depend on activation of both targets together, rather than either one alone [1]. Later work in a transgenic rat model of Alzheimer-like amyloid pathology examined early intervention and cognitive endpoints [2], and human single-ascending-dose research has characterised its pharmacokinetic profile [3]. No therapeutic or clinical claims are made or implied.

Primary Research Areas

• Dual M1 / sigma-1 receptor pharmacology — the defining mechanism — allosteric potentiation at the M1 muscarinic receptor combined with sigma-1 agonism; published work indicates both are required for the observed downstream effects [1].
• Amyloid pathology models — studied in transgenic rat and mouse models for effects on amyloid plaque accumulation and related markers of pathology [2].
• Synaptic density and neuroinflammatory markers — preclinical reports describe changes in synaptic spine density and glial markers in amyloid-pathology rodent models [1].
• Rodent cognitive-behavioural assays — applied in scopolamine-reversal and transgenic-model cognitive tasks to probe M1 and sigma-1 contributions to learning and memory [1,2].
• Early-phase pharmacokinetic characterisation — population pharmacokinetics and food-effect analysis described in single-ascending-dose human research [3].

References

1. Fisher A, Bezprozvanny I, Wu L, Ryskamp DA, Bar-Ner N, Natan N, Brandeis R, Elkon H, Nahum V, Gershonov E, LaFerla FM, Medeiros R. AF710B, a novel M1/σ1 agonist with therapeutic efficacy in animal models of Alzheimer’s disease. Neurodegener Dis. 2016;16(1–2):95–110.
2. Orciani C, Do Carmo S, Foret MK, Hall H, Bonomo Q, Lavagna A, Huang C, Cuello AC. Early treatment with an M1 and sigma-1 receptor agonist prevents cognitive decline in a transgenic rat model displaying Alzheimer-like amyloid pathology. Neurobiol Aging. 2023;132:220–232.
3. Fadiran EO, Hammond E, Tran J, Missling CU, Ette E. Population-based characterization of the pharmacokinetics and food effect of ANAVEX3-71, a novel sigma-1 receptor and allosteric M1 muscarinic receptor agonist. Clin Pharmacol Drug Dev. 2024;13(1):21–31.