(Rac)-AF710B

(Rac)-AF710B is the racemate of AF710B (HY-116586). (Rac)-AF710B is an orally active and blood-brain barrier-penetrant σ1 receptor (σ1R) agonist and M1 muscarinic acetylcholine receptor (M1 mAChR) allosteric agonist. (Rac)-AF710B can be used for research on Alzheimer's disease^[1]. In Vitro:(Rac)-AF710B is a highly potent and selective ligand for M1 mAChR and σ1R, with no significant off-target activity against 83 other GPCRs, ion channels, and transporters^[1].
(Rac)-AF710B (0.1-10 nM; 3 h) significantly enhances the binding affinity of Carbachol (Carbamoylcholine chloride) (HY-B1208) to M1 mAChR and the downstream phosphorylation of p-ERK1/2 and p-CREB in PC12M1 cells at nanomolar concentrations^[1].
(Rac)-AF710B (30 nM) almost completely rescues mushroom spine loss in hippocampal neurons of PS1-KI and APP-KI Alzheimer's disease model mice, an effect that depends on M1 mAChR activation and σ1R expression^[1].
(Rac)-AF710B reduces tau phosphorylation and increases the inactive form of GSK3β in PC12M1 cells through an M1 mAChR-dependent mechanism^[1]. In Vivo:(Rac)-AF710B (1-100 μg/kg; p.o.) is a potent cognitive enhancer in the Trihexyphenidyl (HY-B1277A)-induced passive avoidance impairment model in rats, with significant efficacy at doses of 1-30 μg/kg^[1].
(Rac)-AF710B (10 μg/kg; p.o.) exerts its anti-amnesic effects at least partially through σ₁R activation in the Trihexyphenidyl model, as the σ₁R antagonist NE-100 significantly blocks its cognitive-enhancing effect^[1].
(Rac)-AF710B (10 μg/kg/day; i.p.; for 2 months) alleviates cognitive impairment in the 3xTg-AD mouse model and attenuates AD-like pathological changes, including Aβ accumulation, tau pathology, and neuroinflammation^[1].