title: Recent developments in novel antidepressants targeting α4β2-nicotinic acetylcholine receptors.
abstract: Nicotinic acetylcholine receptors (nAChRs) have been investigated for developing drugs that can potentially treat various central nervous system disorders. Considerable evidence supports the hypothesis that modulation of the cholinergic system through activation and/or desensitization/inactivation of nAChR holds promise for the development of new antidepressants. The introductory portion of this Miniperspective discusses the basic pharmacology that underpins the involvement of α4β2-nAChRs in depression, along with the structural features that are essential to ligand recognition by the α4β2-nAChRs. The remainder of this Miniperspective analyzes reported nicotinic ligands in terms of drug design considerations and their potency and selectivity, with a particular focus on compounds exhibiting antidepressant-like effects in preclinical or clinical studies. This Miniperspective aims to provide an in-depth analysis of the potential for using nicotinic ligands in the treatment of depression, which may hold some promise in addressing an unmet clinical need by providing relief from depressive symptoms in refractory patients.
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago , 833 South Wood Street, Chicago, Illinois 60612, United States.
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Yu
authors.forename: Han-Kun
authors.initials: HK
authors.lastname: Zhang
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Caldarone
authors.forename: J Brek
authors.initials: JB
authors.lastname: Eaton
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Lukas
authors.forename: Alan P
authors.initials: AP
authors.lastname: Kozikowski
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology*; D001384:Azetidines / Q000737:chemistry / Q000494:pharmacology; D001392:Azocines / Q000737:chemistry / Q000494:pharmacology; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D058990:Molecular Targeted Therapy / Q000379:methods; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011807:Quinolizines / Q000737:chemistry / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism*; D000093843:Quinolizidine Alkaloids
chemical_list: D000470:Alkaloids; D000928:Antidepressive Agents; D001384:Azetidines; D001392:Azocines; D008024:Ligands; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011807:Quinolizines; D011978:Receptors, Nicotinic; C104288:A 85380; C403531:nicotinic receptor alpha4beta2; C004712:cytisine; D000093843:Quinolizidine Alkaloids