Varenicline:: An α4β2 nicotinic receptor partial agonist for smoking cessation

被引：742

作者：

Coe, JW ^{[1
]}

Brooks, PR ^{[1
]}

Vetelino, MG ^{[1
]}

Wirtz, MC ^{[1
]}

Arnold, EP ^{[1
]}

Huang, JH ^{[1
]}

Sands, SB ^{[1
]}

Davis, TI ^{[1
]}

Lebel, LA ^{[1
]}

Fox, CB ^{[1
]}

Shrikhande, A ^{[1
]}

Heym, JH ^{[1
]}

Schaeffer, E ^{[1
]}

Rollema, H ^{[1
]}

Lu, Y ^{[1
]}

Mansbach, RS ^{[1
]}

Chambers, LK ^{[1
]}

Rovetti, CC ^{[1
]}

Schulz, DW ^{[1
]}

Tingley, FD ^{[1
]}

O'Neill, BT ^{[1
]}

机构：

[1] Groton Labs, Pfizer Global Res & Dev, Groton, CT 06340 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 10期

关键词：

D O I：

10.1021/jm050069n

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Herein we describe a novel series of compounds from which varenicline (1, 6,7,8,9-tetrahydro-6,10-methano-6H-pyrazino[2,3-h][3]benzazepine) has been identified for smoking cessation. Neuronal nicotinic acetylcholine receptors (nAChRs) mediate the dependence-producing effects of nicotine. We have pursued alpha 4 beta 2 nicotinic receptor partial agonists to inhibit dopaminergic activation produced by smoking while simultaneously providing relief from the craving and withdrawal syndrome that accompanies cessation attempts. Varenicline displays high alpha 4 beta 2 nAChR affinity and the desired in vivo dopaminergic profile.

引用

页码：3474 / 3477

页数：4

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