Advances toward new antidepressants beyond SSRIs: 1-aryloxy-3-piperidinylpropan-2-ols with dual 5-HT1A receptor antagonism/SSRI activities. Part 5.
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.
Takeuchi
Kumiko
K
Lilly Research Laboratories, A Division of Eli Lilly and Company, Indianapolis, IN 46285, USA. ktak@Lilly.com
Kohn
Todd J
TJ
Honigschmidt
Nicholas A
NA
Rocco
Vincent P
VP
Spinazze
Patrick G
PG
Hemrick-Luecke
Susan K
SK
Thompson
Linda K
LK
Evans
David C
DC
Rasmussen
Kurt
K
Koger
Deanna
D
Lodge
David
D
Martin
Laura J
LJ
Shaw
Janice
J
Threlkeld
Penny G
PG
Wong
David T
DT
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
D000928:Antidepressive Agents; D010880:Piperidines; D020005:Propanols; D058829:Serotonin 5-HT1 Receptor Antagonists; D017367:Selective Serotonin Reuptake Inhibitors