Varenicline Hydrochloride (CP 526555) is an orally active partial agonist of the α4β2 nicotinic acetylcholine receptor (α4β2 nAChR, IC50 = 250 nM), which is recognized as the principal mediator of nicotine dependence, and its pharmacological effect is critical in modulating addictive behaviors associated with nicotine exposure. Varenicline Hydrochloride (CP 526555) blocks the direct agonist effects of nicotine on nicotinic acetylcholine receptors while simultaneously stimulating these receptors in a more moderate and controlled manner, making it a widely used research compound in smoking cessation.

α4β2 nAChR:250 nM

Varenicline Hydrochloride (200 μM) treatment of HUVECs for 24 hours showed no significant effect on cell viability [3].
Varenicline Hydrochloride Hydrochloride (100 μM) significantly activated the ERK1/2 and p38 signaling pathways in HUVECs within 30 minutes, and downregulated VE-cadherin expression after 24 hours of treatment[3].
Varenicline Hydrochloride Hydrochloride (100 μM, 4 h) enhanced HUVEC migration capacity by 2.4-fold [3].

In rats, subcutaneous injection of Varenicline Hydrochloride (0.5, 1 mg/kg) dose-dependently reversed fentanyl-induced respiratory depression and mildly attenuated the sedative effects of fentanyl [4]. In adult rhesus monkeys with a history of nicotine and cocaine use, continuous intravenous infusion of Varenicline Hydrochloride (0.004–0.04 mg/kg/h) for 7–10 days, 23 hours per day, dose-dependently reduced self-administration of nicotine and cocaine alone or in combination, without affecting food-rewarded operant responses [5]. In the forced swim test with C57BL/6J and CD-1 mice, oral administration of Varenicline Hydrochloride (0.178–5.6 mg/kg) exhibited antidepressant-like effects [6].