title: Des-keto lobeline analogs with increased potency and selectivity at dopamine and serotonin transporters.
abstract: A series of des-keto lobeline analogs has been synthesized and evaluated for their ability to inhibit the dopamine transporter (DAT) and serotonin transporter (SERT) function and for their affinity for the synaptic vesicle monoamine transporter (VMAT2), as well as for alpha4beta2( *) and alpha7( *) neuronal nicotinic acetylcholine receptors (nAChRs). The enantiomers 8R-hydroxylobel-9-ene (3a) and 10S-hydroxylobel-7-ene (3c) exhibited high potency and selectivity at SERT and DAT, respectively.
authors.affiliation: College of Pharmacy, University of Kentucky, Lexington, 40536-0082, USA.
authors.forename: Guangrong
authors.initials: G
authors.lastname: Zheng
authors.forename: David B
authors.initials: DB
authors.lastname: Horton
authors.forename: Agripina G
authors.initials: AG
authors.lastname: Deaciuc
authors.forename: Linda P
authors.initials: LP
authors.lastname: Dwoskin
authors.forename: Peter A
authors.initials: PA
authors.lastname: Crooks
mesh_terms: D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D008120:Lobeline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D011485:Protein Binding; D011978:Receptors, Nicotinic / Q000378:metabolism; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579167:Chrna7 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D011978:Receptors, Nicotinic; C493452:SLC18A2 protein, human; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; D008120:Lobeline