Cholinergic Receptor System as a Target for Treating Alcohol Abuse and Dependence
Mark A. Prendergast.
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, drug addiction, drug development, nicotinic receptors, pharmacotherapy, translational research, Cholinergic Receptor System , nicotinic receptors, Mecamylamine , nAChR ligands
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