SIB-1553A

SIB-1553A hydrochloride is an orally bioavailable nicotinic acetylcholine receptors (nAChRs) agonist, with selectivity for β4 subunit-containing nAChRs. SIB-1553A hydrochloride is also a selective neuronal nAChR ligand. SIB-1553A hydrochloride is a cognitive enhancer, and has therapeutic potential for the symptomatic treatment of Alzheimer’s disease and other cognitive disorders[1][2].

Signaling Pathways >> Membrane Transporter/Ion Channel >> nAChR

Signaling Pathways >> Neuronal Signaling >> nAChR

Research Areas >> Neurological Disease

SIB-1553A hydrochloride displaces the binding of [H]nicotine (NIC) to the rat brain nAChRs with an IC50 value of 110 nM[1]. In calcium flux assays, SIB-1553A hydrochloride (0.1-5 μM), shows a greater selectivity for beta4-subunit containing recombinant hnAChRs (alpha2beta4, alpha3beta4 and alpha4beta4) vs. beta2-subunit containing nAChRs (alpha4beta2 and alpha3beta2) both in terms of efficacy and potency[2].

SIB-1553A hydrochloride (1-40 mg/kg; s.c.) produces dose-dependent increases in ACh levels[3]. Animal Model: Male Sprague-Dawley rats (200-250 g)[3] Dosage: 1, 2, 4, 10, 20 and 40 mg/kg Administration: s.c. Result: Induced hippocampal ACh release.

[1]. Vernier JM, et al. 4-[[2-(1-Methyl-2-pyrrolidinyl)ethyl]thio]phenol hydrochloride (SIB-1553A): a novel cognitive enhancer with selectivity for neuronal nicotinic acetylcholine receptors. J Med Chem. 1999 May 20;42(10):1684-6.

[2]. Rao TS, et al. In vitro pharmacological characterization of (+/-)-4-[2-(1-methyl-2-pyrrolidinyl)ethyl]thio]phenol hydrochloride (SIB-1553A), a nicotinic acetylcholine receptor ligand. Brain Res. 2003 Aug 15;981(1-2):85-98.

[3]. Rao TS, et al. In vivo pharmacological characterization of (+/-)-4-[2-(1-methyl-2-pyrrolidinyl)ethyl]thiophenol hydrochloride (SIB-1553A), a novel cholinergic ligand: microdialysis studies. Brain Res. 2003 Oct 3;986(1-2):71-81.