Abstract
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 alpha4beta2 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 alpha4beta2 nAChR affinity and the desired in vivo dopaminergic profile.
MeSH terms
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Animals
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Benzazepines / chemical synthesis*
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Benzazepines / chemistry
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Benzazepines / pharmacology
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Cell Line
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Cerebral Cortex / drug effects
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Cerebral Cortex / metabolism
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Humans
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In Vitro Techniques
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Nicotinic Agonists / chemical synthesis*
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Nicotinic Agonists / chemistry
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Nicotinic Agonists / pharmacology
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Oocytes / drug effects
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Oocytes / physiology
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Quinoxalines / chemical synthesis*
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Quinoxalines / chemistry
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Quinoxalines / pharmacology
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Radioligand Assay
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Rats
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Receptors, Nicotinic / drug effects*
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Receptors, Nicotinic / physiology
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Smoking Cessation / methods*
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Varenicline
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Xenopus laevis
Substances
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Benzazepines
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Nicotinic Agonists
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Quinoxalines
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Receptors, Nicotinic
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nicotinic receptor alpha4beta2
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Varenicline