Varenicline Tartrate (CP 526555-18) is a benzazepine derivative that functions as an ALPHA4/BETA2 NICOTINIC RECEPTOR partial agonist. It is used for SMOKING CESSATION.

Varenicline在表达nAChRs的HEK细胞中对alpha4beta2 nAChRs显示出部分激动性，其最大效能为尼古丁的45%。[1] Varenicline是一种强效的alpha4beta2受体部分激动剂，具有2.3 mM的EC50和相对于乙酰胆碱的13.4%的效能。在alpha3beta4受体上，Varenicline的潜力较低但效能更高，其EC50为55 mM，效能为75%。[2]

Varenicline 在刺激大鼠大脑切片中的[(3)H]-多巴胺释放以及增加大鼠伏隔核内多巴胺释放的效能方面，明显低于尼古丁（40-60％），但其潜力却超过尼古丁。Varenicline 有效减弱尼古丁引起的多巴胺释放至仅与Varenicline 单独作用时的效果相一致，显示出部分激动剂的特性。此外，Varenicline 减少了大鼠对尼古丁的自我给药行为，并比尼古丁有更低的自我给药断点。Varenicline 降低尼古丁自我给药的能力呈剂量依赖性，并减弱了尼古丁引起的以及尼古丁诱发加尼古丁配对提示引起的复吸。作为alpha4beta2 nAChRs的部分激动剂，Varenicline 减少尼古丁摄入量，并已被新近批准用作戒烟辅助。Varenicline 选择性降低乙醇而非蔗糖的寻求行为，是通过一种自主自给饮酒范式，并在动物长期暴露于乙醇2个月后开始Varenicline 治疗，也降低了自愿乙醇消费量而不影响水消费量。

Kinase inhibition: Vandetanib is incubated with enzyme, 10 mM MnCl2, and 2 μM ATP in 96-well plates coated with a poly(Glu, Ala, Tyr) 6:3:1 random copolymer substrate. Phosphorylated tyrosine is then detected by sequential incubation with a mouse IgG anti-phosphotyrosine 4 g10 antibody, a horseradish peroxidase-linked sheep antimouse immunoglobulin antibody, and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid). This methodology is adapted to examine selectivity versus tyrosine kinases associated with EGFR, PDGFRβ, Tie-2, FGFR1, c-kit, erbB2, IGF-1R, and FAK. All enzyme assays (tyrosine or serine-threonine) used appropriate ATP concentrations at or just below the respective Km (0.2–14 μM). Selectivity versus serine-threonine kinases (CDK2, AKT, and PDK1) is examined using a relevant scintillation proximity-assay (SPA) in 96-well plates. CDK2 assays contained 10 mM MnCl2, 4.5 μM ATP, 0.15 μCi of [γ-33 P]ATP/reaction, 50 mM HEPES (pH 7.5), 1 mM DTT, 0.1 mM sodium orthovanadate, 0.1 mM sodium fluoride, 10 mM sodium glycerophosphate, 1 mg/mL BSA fraction V, and a retinoblastoma substrate (part of the retinoblastoma gene, 792–928, expressed in a glutathione S-transferase expression system; 0.22 μM final concentration). Reactions are allowed to proceed at room temperature for 60 minutes before quenching for 2 hours with 150 μL of a solution containing EDTA (62 mM final concentration), 3 μg of a rabbit immunoglobulin anti-glutathione S-transferase antibody and protein A SPA-polyvinyltoluene beads (0.8 mg/reaction). Plates are then sealed, centrifuged (1200× g for 5 minutes), and counted on a Microplate scintillation counter for 30 seconds.