Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors.

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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 ID

16766716 [ View in PubMed

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Abstract

Varenicline, a new nicotinic ligand based on the structure of cytisine, has recently been approved by the U.S. Food and Drug Administration for use as a smoking cessation aid. Varenicline has been shown to be a partial agonist of alpha4beta2 receptors, and in equilibrium binding assays, it is highly selective for the alpha4beta2 receptor. In this study, we have examined the functional activity of varenicline at a variety of rat neuronal nicotinic receptors expressed in Xenopus laevis oocytes and assayed under two-electrode voltage clamp. We also find that varenicline is a potent, partial agonist at alpha4beta2 receptors, with an EC50 of 2.3 +/- 0.3 microM and an efficacy (relative to acetylcholine) of 13.4 +/- 0.4%. Varenicline has lower potency and higher efficacy at alpha3beta4 receptors, with an EC50 of 55 +/- 8 microM and an efficacy of 75 +/- 6%. Varenicline also seems to be a weak partial agonist at alpha3beta2 and alpha6-containing receptors, with an efficacy <10%. It is remarkable that varenicline is a potent, full agonist at alpha7 receptors with an EC50 of 18 +/- 6 microM and an efficacy of 93 +/- 7% (relative to acetylcholine). Thus, whereas varenicline is a partial agonist at some heteromeric neuronal nicotinic receptors, it is a full agonist at the homomeric alpha7 receptor. Some combination of these actions may be involved in the mechanism of varenicline as a smoking cessation aid.

DrugBank Data that Cites this Article

Drugs

Varenicline

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Varenicline	Neuronal acetylcholine receptor subunit alpha-3	Protein	Humans	Unknown	Partial agonist	Details
Varenicline	Neuronal acetylcholine receptor subunit alpha-6	Protein	Humans	Unknown	Partial agonist	Details
Varenicline	Neuronal acetylcholine receptor subunit alpha-7	Protein	Humans	Unknown	Agonist	Details