Sabcomeline (hydrochloride)

Sabcomeline hydrochloride is a muscarinic receptor agonist capable of crossing the blood-brain barrier. Sabcomeline hydrochloride exhibits affinity for all hM1 to hM5 subtypes (pK_i=6.72-7.23), and shows near-full agonism at the hM3 receptor, inducing extracellular acidification. Sabcomeline hydrochloride alters the binding kinetics of dopamine D2 receptors through neural network regulation. Sabcomeline hydrochloride also causes minimal cardiovascular changes, effectively reverses spatial memory deficits in rodents and induces conditioned taste aversion. Sabcomeline hydrochloride is an important tool compound in studies of Alzheimer's disease and related neurodegenerative diseases^[1][2][3]. IC50 & Target:Muscarinic M1 receptor^[1][2] In Vitro:Compared with Carbamoylcholine (HY-B1208), Sabcomeline hydrochloride exhibits the lowest potency (≈20%) at the hM₁ and hM₅ subtypes; moderate potency at the hM₄ (≈38%) and hM₂ (≈57%) subtypes; and the highest partial agonist potency (≈70%) at the hM₃ subtype^[1]. In Vivo:Sabcomeline hydrochloride (0.01-3 mg/kg; i.v.; 0.3 mg/kg; i.p.) exhibits dose-dependent, non-M₁-selective mACh receptor binding in mouse brain and heart with rapid dissociation (return to control levels by 3-4 hours post-0.3 mg/kg i.v. dose), and alters striatal dopamine D₂ receptor binding kinetics by decreasing [³H]NMSP k₃ by ~15% and increasing [³H]raclopride BP by ~20%^[2].
Sabcomeline hydrochloride (0.03-0.1 mg/kg; i.p.; single dose 15 minutes prior to testing) significantly reverses 20-s delay-induced T-maze choice accuracy deficits in male Hooded Lister rats, with cholinergic side effects appearing at higher doses of 0.3 mg/kg and above^[3].
Sabcomeline hydrochloride (0.3-1.0 mg/kg; i.p.; single dose 15 minutes after saccharin exposure) induces significant conditioned taste aversion in male Hooded Lister rats at a minimum effective dose of 0.3 mg/kg, with 60% inhibition of saccharin intake observed at 1.0 mg/kg^[3].