用户名： 密   码：
注册 | 忘记密码？
药品详细

Varenicline(伐尼克兰)

化学结构式图
中文名
伐尼克兰
英文名
Varenicline
分子式
C13H13N3
化学名
(1R,12S)-5,8,14-triazatetracyclo[10.3.1.0^{2,11}.0^{4,9}]hexadeca-2(11),3,5,7,9-pentaene
分子量
Average: 211.2624
Monoisotopic: 211.110947431
CAS号
249296-44-4
ATC分类
N07B 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Varenicline is a prescription medication used to treat smoking addiction. This medication is the first approved nicotinic receptor partial agonist. Specifically, varenicline is a partial agonist of the alpha4/beta2 subtype of the nicotinic acetylcholine receptor. In addition it acts on alpha3/beta4 and weakly on alpha3beta2 and alpha6-containing receptors. A full agonism was displayed on alpha7-receptors.

生产厂家
  • Pfizer inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, Billing CB, Gong J, Reeves KR: Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA. 2006 Jul 5;296(1):56-63. Pubmed
  2. Mihalak KB, Carroll FI, Luetje CW: 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. Pubmed
  3. Obach RS, Reed-Hagen AE, Krueger SS, Obach BJ, O’Connell TN, Zandi KS, Miller S, Coe JW: Metabolism and disposition of varenicline, a selective alpha4beta2 acetylcholine receptor partial agonist, in vivo and in vitro. Drug Metab Dispos. 2006 Jan;34(1):121-30. Epub 2005 Oct 12. Pubmed
  4. Coe JW, Brooks PR, Vetelino MG, Wirtz MC, Arnold EP, Huang J, Sands SB, Davis TI, Lebel LA, Fox CB, Shrikhande A, Heym JH, Schaeffer E, Rollema H, Lu Y, Mansbach RS, Chambers LK, Rovetti CC, Schulz DW, Tingley FD 3rd, O’Neill BT: Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation. J Med Chem. 2005 May 19;48(10):3474-7. Pubmed
  5. Kuehn BM: FDA speeds smoking cessation drug review. JAMA. 2006 Feb 8;295(6):614. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Phenylpiperidines
  • Benzazepines
Substructures
  • Indanes
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Phenylpiperidines
  • Pyrazines
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Benzazepines
  • Quinoxalines
  • Piperidines
适应症
药理
Indication For use as an aid in smoking cessation.
Pharmacodynamics Varenicline is a partial nicotinic acetylcholine receptor agonist, designed to partially activate this system while displacing nicotine at its sites of action in the brain.
Mechanism of action Varenicline is an alpha-4 beta-2 neuronal nicotinic acetylcholine receptor partial agonist. The drug shows high selectiviyty for this receptor subclass, relative to other nicotinic receptors (>500-fold alpha-3 beta-4, >3500-fold alpha-7, >20,000-fold alpha-1 beta gamma delta) or non-nicotinic receptors and transporters (>2000-fold). The drug competitively inhibits the ability of nicotine to bind to and activate the alpha-4 beta-2 receptor. The drug exerts mild agonistic activity at this site, though at a level much lower than nicotine; it is presumed that this activation eases withdrawal symptoms.
Absorption Not Available
Volume of distribution Not Available
Protein binding Less than 20%.
Metabolism
Metabolism is limited (<10%). Most of the active compound is excreted renally (81%). A small proportion is glucuronidated, oxidated, N-formylated or conjugated to a hexose.
Route of elimination Varenicline undergoes minimal metabolism, with 92% excreted unchanged in the urine. Renal elimination of varenicline is primarily through glomerular filtration along with active tubular secretion possibly via the organic cation transporter, OCT2.
Half life The elimination half-life of varenicline is approximately 24 hours
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
logP 0.9 Not Available
Predicted Properties
Property Value Source
water solubility 8.77e-02 g/l ALOGPS
logP 1.39 ALOGPS
logP 1.01 ChemAxon
logS -3.4 ALOGPS
pKa (strongest basic) 9.73 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 37.81 ChemAxon
rotatable bond count 0 ChemAxon
refractivity 61.3 ChemAxon
polarizability 23.12 ChemAxon
药物相互作用
食物相互作用
Not Available

返回 | 收藏