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Cholinergic Receptor System as a Target for Treating Alcohol Abuse and Dependence

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Abstract:

Alcohol dependence and other alcohol use disorders are major public health problems. Due to the limitations in efficacy with current medications for the management of alcohol abuse and dependence, there is a need for alterantive pharmacotherapies. Emerging preclinical and clinical data indicate that brain nicotinic acetylcholine receptors (nAChRs), a heterogeneous family of ion channels expressed in the mammalian brain, are critical targets for the development of pharmacotherapies for alcohol abuse and dependence. Evidence suggests that the effects of nAChR partial agonists and antagonists have promise for the management of alcohol dependence and other alcohol use disorders. The present review summarizes information on the most recent pharmacotherapies targeting nAChRs, including cytisine, sazetidine A, varenicline, lobeline mecamylamine, PF-4575180 and CP-601932, that are able to treat alcohol dependence. The role of α4β2*, α3β4* and/or other subtypes associated effects in reducing voluntary alcohol consumption or modulate alcohol drinking behavior in animal models and humans are reviewed. Patents discussed include those targeting α4β2* and α7 subtypes as well as cholinesterase inhibitors. Future research indicating the ability of nAChR based compounds to reduce alcohol consumption or modulate alcohol drinking behavior in preclinical and clinical studies, are also discussed.

Keywords: Alcohol dependence; Cholinergic Receptor System; Mecamylamine; drug addiction; drug development; nAChR ligands; nicotinic receptors; pharmacotherapy; translational research

Document Type: Research Article

DOI: https://doi.org/10.2174/157488912800673173

Affiliations: Department of Pharmaceutical Sciences, College of Pharmacy, Box 2202C, South Dakota State University, Avera Health and Science Center, SAV 265, Brookings, SD 57007, USA.

Publication date: 2012-08-01

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  • Recent Patents on CNS Drug Discovery publishes review articles on recent patents in the field of CNS drug discovery e.g. novel bioactive compounds, analogs & targets. A selection of important and recent patents on CNS drug discovery is also included in the journal. The journal is essential reading for all researchers involved in CNS drug design and discovery.
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