Varenicline-¹⁵N,¹³C,d₂  (Synonyms: 伐尼克兰-¹⁵N,¹³C,d₂; CP 526555-15N,13C,d2)

Varenicline-¹⁵N,¹³C,d₂ is ¹⁵N and deuterated labeled Varenicline (HY-10019). Varenicline (CP 526555) is an orally active partial agonist of α4β2 nicotinic acetylcholine receptor (α4β2 nAChR, IC₅₀=250 nM), which is the principal mediator of nicotine dependence. Varenicline is also a partial agonist of α6β2 nAChR and a full agonist of α6β2 nAChR. Varenicline blocks the direct agonist effects of nicotine on nAChR while stimulates nAChR in a more moderate way, being widely used as an aid of smoking cessation^{[1][2][3][4][5]}.

氢、碳和其他元素的稳定重同位素已被纳入药物分子中，主要作为药物开发过程中定量的示踪剂。氘化引起了人们的关注，因为它可能影响药物的药代动力学和代谢谱^[1]。
Varenicline (200 μM, 24 h) 对 HUVEC 细胞活力无明显影响^[4]。
Varenicline (100 μM, 30 min) 显著激活 HUVEC 细胞中的 ERK1/2 和 p38 信号通路，因而Varenicline (100 μM, 24 h) 降低 HUVEC 细胞中 VE-cadherin 的表达^[4]。
Varenicline (100 μM, 4 h) 促进 HUVEC 细胞 2.4 倍的细胞迁移^[4]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Varenicline (0.5, 1mg/kg, 皮下注射, 即刻给药) 剂量依赖性地逆转芬太尼引起的大鼠呼吸抑制，同时轻度缓解芬太尼的镇静效果^[5]。
Varenicline (0.004–0.04 mg/kg/h, 静脉滴注, 一日 23h, 7-10 d) 剂量依赖性地减少有可卡因和尼古丁使用经验的成年恒河猴对尼古丁 (0.0032 mg/kg/inj) 单独使用，以及与可卡因 (0.0032 mg/kg/inj) 联合使用的自我给药水平，且对食物维持反应无显著影响^[6]。
Varenicline (0.178-5.6 mg/kg, 口服, 即刻给药) 在 C57BL/6J 和 CD-1 小鼠的强迫游泳实验中显示出抗抑郁样活性^[7]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

215.26

C₁₂¹³CH₁₁D₂N₂¹⁵N

249296-44-4

伐尼克兰-¹⁵N,¹³C,d₂

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216.  [Content Brief]

  [2]. Koegelenberg CF, et al. Efficacy of varenicline combined with nicotine replacement therapy vs varenicline alone for smoking cessation: a randomized clinical trial. JAMA. 2014 Jul;312(2):155-61.  [Content Brief]

  [3]. Magnus CJ, et al. Ultrapotent chemogenetics for research and potential clinical applications. Science. 2019;364(6436):eaav5282.  [Content Brief]

  [4]. Koga M, 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;390:1-9.  [Content Brief]

  [5]. Ren J, et al. Countering Opioid-induced Respiratory Depression in Male Rats with Nicotinic Acetylcholine Receptor Partial Agonists Varenicline and ABT 594. Anesthesiology. 2020 May;132(5):1197-1211.  [Content Brief]

  [6]. Mello NK, et al. Effects of chronic varenicline treatment on nicotine, cocaine, and concurrent nicotine+cocaine self-administration. Neuropsychopharmacology. 2014 Apr;39(5):1222-31.  [Content Brief]

  [7]. Rollema H, et al. Varenicline has antidepressant-like activity in the forced swim test and augments sertraline's effect. Eur J Pharmacol. 2009 Mar 1;605(1-3):114-6.  [Content Brief]