Varenicline (CP 526555) dihydrochloride

Varenicline (CP 526555) dihydrochloride is a potent partial agonist for α4β2 nicotinic acetylcholine receptor (nAChR) with an EC50 value of 2.3 μM. Varenicline dihydrochloride is a full agonist for α3β4 and α7 nAChRs with EC50 values of 55 μM and 18 μM, respectively[2]. Varenicline dihydrochloride is a nicotinic ligand based on the structure of cytosine, and has the potential for smoking cessation treatment[5].

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

Signaling Pathways >> Neuronal Signaling >> nAChR

Research Areas >> Inflammation/Immunology

Research Areas >> Neurological Disease

EC50: 2.3 μM (α4β2 nAChR); 18 μM (α7 nAChR); 55 μM (α3β4 nAChR)[2]

Varenicline dihydrochloride (1 μM, 24 h ) inhibits LPS-Induced cytokine secretions (IL-1β, IL-6, and TNF α) and cell proliferation rate in RAW 264.7 macrophages[1]. Varenicline dihydrochloride (250 nM) evokes action potentials (Aps) in the absence of ACh stimulation in Human adrenal chromaffin cells isolated from male and female organ donors[3]. Varenicline dihydrochloride (100 μM, 4 h) promotes migration of HUVECs by lowering the protein expression of VE-cadherin[4]. Cell Proliferation Assay[1] Cell Line: RAW 264.7 murine macrophage cells (treated with 4 μg/mL LPS for 24 h) Concentration: 1 μM Incubation Time: 0-48 h Result: Decreased the LPS-induced cell proliferation rate. Western Blot Analysis[4] Cell Line: HUVECs Concentration: 1, 10, 100 μM Incubation Time: 24 h or 30 min Result: Decreased the protein expression of VE-cadherin and activated ERK1/2, p38 and JNK signaling.

Varenicline dihydrochloride (Subcutaneous injection, 0.01-1 mg/kg, 3 days) given 10 min prior to nicotine (0.5 mg/kg, s.c.) inhibits nicotine conditioned place preference (CPP)[5]. Varenicline dihydrochloride (Subcutaneous injection, 2.5 mg/kg, 3 days) results in a place aversion which is dependent on α5 nAChRs but not β2 nAChRs[5]. Varenicline dihydrochloride (Subcutaneous injection, 0.1 and 0.5 mg/kg, 3 days) reverses nicotine withdrawal signs such as hyperalgesia and somatic signs and withdrawal-induced aversion in a dose-related manner[5]. Animal Model: ICR male mice[5] Dosage: 0.01-1 mg/kg for 3 days Administration: Subcutaneous injection Result: Inhibited nicotine conditioned place preference (CPP) in a dose dependent manner.

[1]. Elif Baris, et al. Varenicline Prevents LPS-Induced Inflammatory Response via Nicotinic Acetylcholine Receptors in RAW 264.7 Macrophages. Front Mol Biosci. 2021 Oct 12;8:721533.

[2]. Mihalak KB, et al. Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors.Mol Pharmacol. 2006 Sep;70(3):801-5. Epub 2006 Jun 9.

[3]. Jin H, et al. Therapeutic concentrations of varenicline in the presence of nicotine increase action potential firing in human adrenal chromaffin cells. J Neurochem. 2017 Jan;140(1):37-52.

[4]. Mitsuhisa Koga, et al. Varenicline promotes endothelial cell migration by lowering vascular endothelial-cadherin levels via the activated α7 nicotinic acetylcholine receptor-mitogen activated protein kinase axis. Toxicology. 2017 Sep 1;390:1-9.

[5]. Bagdas D, et al. New insights on the effects of varenicline on nicotine reward, withdrawal and hyperalgesia in mice.Neuropharmacology. 2018 Aug;138:72-79.