title: Advances toward new antidepressants beyond SSRIs: 1-aryloxy-3-piperidinylpropan-2-ols with dual 5-HT1A receptor antagonism/SSRI activities. Part 5.
abstract: A series of 1-aryloxy-3-piperidinylpropan-2-ols possessing potent dual 5-HT1A receptor antagonism and serotonin reuptake inhibition was discovered. 1-(1H-Indol-4-yloxy)-3-(4-benzo[b]thiophen-2-ylpiperidinyl)propan-2-ols exhibited selective and high affinities at the 5-HT1A receptor and serotonin reuptake site in vitro. In vivo evaluation of this series of compounds demonstrated elevated extracellular serotonin levels from the basal and quick recovery of neuron firing that was presumably suppressed by the initial acute activation of 5-HT1A somatodendritic autoreceptors.
authors.affiliation: Lilly Research Laboratories, A Division of Eli Lilly and Company, Indianapolis, IN 46285, USA. ktak@Lilly.com
authors.forename: Kumiko
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Kohn
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Honigschmidt
authors.forename: Vincent P
authors.initials: VP
authors.lastname: Rocco
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Spinazze
authors.forename: Susan K
authors.initials: SK
authors.lastname: Hemrick-Luecke
authors.forename: Linda K
authors.initials: LK
authors.lastname: Thompson
authors.forename: David C
authors.initials: DC
authors.lastname: Evans
authors.forename: Kurt
authors.initials: K
authors.lastname: Rasmussen
authors.forename: Deanna
authors.initials: D
authors.lastname: Koger
authors.forename: David
authors.initials: D
authors.lastname: Lodge
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Martin
authors.forename: Janice
authors.initials: J
authors.lastname: Shaw
authors.forename: Penny G
authors.initials: PG
authors.lastname: Threlkeld
authors.forename: David T
authors.initials: DT
authors.lastname: Wong
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D066298:In Vitro Techniques; D008297:Male; D008968:Molecular Conformation; D010880:Piperidines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D020005:Propanols / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D058829:Serotonin 5-HT1 Receptor Antagonists; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000928:Antidepressive Agents; D010880:Piperidines; D020005:Propanols; D058829:Serotonin 5-HT1 Receptor Antagonists; D017367:Selective Serotonin Reuptake Inhibitors