title: From ligand design to therapeutic efficacy: the challenge for nicotinic receptor research.
abstract: S-Nicotine, the principal psychoactive constituent of Nicotiana tabacum, underpins addiction to tobacco smoking. Although tobacco consumption is a leading cause of death worldwide, nicotine itself is also proposed to have potential therapeutic benefits for a diverse range of conditions. Nicotine interacts with its cognate receptors in the central nervous system to exert a predominantly modulatory influence, making neuronal nicotinic receptors attractive therapeutic targets. Here, we focus on three natural products as lead compounds for drug discovery programs, nicotine, epibatidine and cytisine, and consider the aims and limitations that shape these drug discovery endeavors.
authors.affiliation: Department of Chemistry, Faculty of Sciences, University of Chile, Casilla 653, Santiago, Chile. bcassels@uchile.cl
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Cassels
authors.forename: Isabel
authors.initials: I
authors.lastname: Bermúdez
authors.forename: Federico
authors.initials: F
authors.lastname: Dajas
authors.forename: J Andrés
authors.initials: JA
authors.lastname: Abin-Carriquiry
authors.forename: Susan
authors.initials: S
authors.lastname: Wonnacott
mesh_terms: D000470:Alkaloids; D000818:Animals; D001392:Azocines; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015195:Drug Design; D006801:Humans; D008024:Ligands; D009538:Nicotine; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011725:Pyridines; D011807:Quinolizines; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013329:Structure-Activity Relationship; D000093843:Quinolizidine Alkaloids
chemical_list: D000470:Alkaloids; D001392:Azocines; D019086:Bridged Bicyclo Compounds, Heterocyclic; D008024:Ligands; D009538:Nicotine; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011725:Pyridines; D011807:Quinolizines; D011978:Receptors, Nicotinic; C004712:cytisine; D000093843:Quinolizidine Alkaloids; C082748:epibatidine