<p>Varenicline binds with high&nbsp;affinity&nbsp;and selectivity at &alpha;4&beta;2 neuronal nicotinic acetylcholinereceptors. The efficacy of Varenicline in smoking cessation is believed to be the result of varenicline&#39;s activity at &alpha;4&beta;2&nbsp;sub-type of the nicotinic receptor where its binding produces&nbsp;agonist&nbsp;activity, while simultaneously preventing nicotine binding to these receptors.<br />
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Electrophysiology&nbsp;studies in vitro and neurochemical studies&nbsp;in vivo&nbsp;have shown that varenicline binds to &alpha;4&beta;2 neuronal nicotinic acetylcholine receptors and stimulates receptor-mediated activity, but at a significantly lower level than nicotine. Varenicline blocks the ability of nicotine to activate &alpha;4&beta;2 receptors and thus to stimulate the central nervous mesolimbic dopamine&nbsp;system, believed to be the neuronal mechanism underlying reinforcement and reward experienced upon smoking. Varenicline is highly selective and binds more potently to &alpha;4&beta;2 receptors than to other common nicotinic receptors ( &gt;500-fold &alpha;3&beta;4, &gt;3,500fold &alpha;7, &gt;20,000-fold &alpha;1&beta;&gamma;&delta;), or to non-nicotinic receptors and transporters (&gt; 2,000-fold). Varenicline also binds with moderate affinity (Ki = 350 nM) to the 5-HT3 receptor.</p>