AF710B

AF710B belongs to a family of cholinergic compounds designed to engage the M1 subtype of muscarinic receptor selectively while also activating the sigma-1 receptor, a chaperone protein involved in cellular stress responses ^[1]. The dual M1 and sigma-1 profile is central to its rationale: M1 signaling is important for memory and can shift processing of the amyloid precursor protein, while sigma-1 activation supports neuronal resilience ^[1]. It was later licensed and developed by Anavex Life Sciences under the name ANAVEX3-71 ^[3][4].

The most striking preclinical findings concern its apparent disease-modifying activity. In transgenic rat models of Alzheimer-like amyloid pathology, chronic low-dose oral treatment reversed cognitive deficits even when started at advanced disease stages, and the benefits persisted for weeks after the drug was withdrawn; these effects were accompanied by reductions in amyloid burden and neuroinflammation, increased clearance of amyloid into cerebrospinal fluid, and higher levels of a synaptic marker ^[1]. A separate study showed that starting treatment early, before plaque formation, prevented cognitive decline, lowered amyloid plaques and Aβ peptide levels, reduced microglial and astrocyte activation, and restored the maturation of brain-derived neurotrophic factor ^[2].

AF710B has entered early human testing under the name ANAVEX3-71, with development directed at frontotemporal dementia, schizophrenia, and Alzheimer's disease ^[3][4]. In a first-in-human single-ascending-dose study, it showed linear, dose-proportional pharmacokinetics with a relatively short half-life and no clinically meaningful effect on cardiac ECG measures such as the QTc interval, and food did not affect its absorption ^[3][4]. It remains an investigational agent and is not an approved medicine or a marketed supplement ^[3][4].

AF710B is research-grade with no approved consumer use and essentially no safety profile for how people actually buy and use it; it is an unscheduled research chemical in most countries, though that varies. First, do not misread the potency numbers: the picomolar figure is an in-vitro EC50, not the dose you swallow, which sits in the milligram range, so this is not a microgram-weighing situation. Cholinergic overshoot is still the real risk (slow heart rate, heavy secretions, bronchospasm, gut cramping), so go low and slow. One practical catch on availability: making genuinely pure AF710B, or clean (+) or (-) AF710 with none of the other regioisomers riding along, is almost certainly expensive enough that a legitimately resolved product is impractical to sell at nootropic prices, so most of what circulates is unlikely to be the clean single isomer. Skip it in pregnancy.

AF710B was developed by the medicinal chemist Abraham Fisher at the Israel Institute for Biological Research in Ness Ziona, extending his long-running program of selective muscarinic agonists aimed at Alzheimer's disease. The molecule was characterized as a highly potent, selective agent that acts as a positive allosteric modulator at the M1 muscarinic receptor and as a direct agonist at the sigma-1 receptor. Preclinical studies published in the mid-2010s reported that it attenuated cognitive deficits and reduced amyloid and neuroinflammatory hallmarks in transgenic mouse and rat models of the disease, with effects described as long-lasting and potentially disease-modifying. The compound was subsequently taken up by Anavex Life Sciences, where it is designated ANAVEX 3-71, and Fisher joined that company's scientific advisory board; it has remained in early-stage development.