Varenicline (CP 526555) is a selective partial agonist of the α4β2 nAChR and a full agonist of the α3β4 nAChR and α7 nAChR to help smokers with cardiovascular disease and COPD quit smoking.

Varenicline treatment at a concentration of 200 μM for 24 hours has no significant effect on the viability of HUVEC cells. At a concentration of 100 μM for 30 minutes, Varenicline significantly activates the ERK1/2 and p38 signaling pathways in HUVEC cells, which subsequently leads to reduced expression of VE-cadherin after 24 hours of treatment at the same concentration. Additionally, Varenicline treatment at 100 μM for 4 hours promotes a 2.4-fold increase in HUVEC cell migration.[3]

Varenicline administered subcutaneously at doses of 0.5 and 1 mg/kg immediately reversed fentanyl-induced respiratory depression in rats in a dose-dependent manner and mildly alleviated the sedative effects of fentanyl. [4]
Additionally, when administered via intravenous infusion at 0.004–0.04 mg/kg/h for 23 hours per day over 7–10 days, Varenicline dose-dependently reduced self-administration of nicotine (0.0032 mg/kg/injection) alone and in combination with cocaine (0.0032 mg/kg/injection) in adult rhesus monkeys with a history of cocaine and nicotine use, without significantly affecting food-maintained responses. [5]
Moreover, Varenicline given orally at doses of 0.178–5.6 mg/kg, demonstrated antidepressant-like effects in the forced swim test in both C57BL/6J and CD-1 mice. [6]