Behavioral and Neurochemical Effects of 5-{4-[4-(5-Cyano-3-indolyl)-butyl)-butyl]-1-piperazinyl}-benzofuran-2-carboxamide (EMD 68843): A Combined Selective Inhibitor of Serotonin Reuptake and 5-Hydroxytryptamine1A Receptor Partial Agonist
@article{Page2002BehavioralAN, title={Behavioral and Neurochemical Effects of 5-\{4-[4-(5-Cyano-3-indolyl)-butyl)-butyl]-1-piperazinyl\}-benzofuran-2-carboxamide (EMD 68843): A Combined Selective Inhibitor of Serotonin Reuptake and 5-Hydroxytryptamine1A Receptor Partial Agonist}, author={Michelle E. Page and John F. Cryan and A. O. Sullivan and Ashutosh Dalvi and Berangere Saucy and David R Manning and Irwin Lucki}, journal={Journal of Pharmacology and Experimental Therapeutics}, year={2002}, volume={302}, pages={1220 - 1227} }
5-{4-[4-(5-Cyano-3-indolyl)-butyl)-butyl]-1-piperazinyl}-benzofuran-2-carboxamide (EMD 68843; vilazodone) is a novel compound with combined high affinity and selectivity for the 5-hydroxytryptamine (5-HT) transporter and 5-HT1A receptors. EMD 68843 was tested as a prototype compound, which benefits from dual pharmacological effects that could increase extracellular 5-HT to levels higher than those produced by conventional selective serotonin reuptake inhibitors (SSRIs). In Sf9 cells, EMD 68843…
87 Citations
Dual 5-HT1A agonists and 5-HT re-uptake inhibitors by combination of indole-butyl-amine and chromenonyl-piperazine structural elements in a single molecular entity.
- Chemistry, BiologyBioorganic & medicinal chemistry
- 2004
Neurochemical evaluation of the novel 5-HT1A receptor partial agonist/serotonin reuptake inhibitor, vilazodone.
- Biology, ChemistryEuropean journal of pharmacology
- 2005
Studies toward the discovery of the next generation of antidepressants. Part 6: Dual 5-HT1A receptor and serotonin transporter affinity within a class of arylpiperazinyl-cyclohexyl indole derivatives.
- Chemistry, BiologyBioorganic & medicinal chemistry
- 2008
Novel 4-aryl-pyrido[1,2-c]pyrimidines with dual SSRI and 5-HT(1A) activity. Part 5.
- Chemistry, BiologyEuropean journal of medicinal chemistry
- 2015
Electrophysiological evidence for rapid 5-HT₁A autoreceptor inhibition by vilazodone, a 5-HT₁A receptor partial agonist and 5-HT reuptake inhibitor.
- BiologyEuropean journal of pharmacology
- 2013
Synthesis and biological evaluation of novel pyrrolidine-2,5-dione derivatives as potential antidepressant agents. Part 1.
- Chemistry, BiologyEuropean journal of medicinal chemistry
- 2013
Mechanism of action of the bimodal antidepressant vilazodone: evidence for serotonin1A-receptor-mediated auto-augmentation of extracellular serotonin output
- Biology, ChemistryPsychopharmacology
- 2013
In spite of high intrinsic 5-HT1A activity in reserpinized rats, the net effect of vilazodone at release-regulating 5- HT1A autoreceptors must be inhibitory, leading to markedly increased 5-ht output.
Effect of vilazodone on 5-HT efflux and re-uptake in the guinea-pig dorsal raphe nucleus.
- BiologyEuropean journal of pharmacology
- 2005
Involvement of kynurenine pathway and N-methyl-d-aspartate receptors in the antidepressant-like effect of vilazodone in the tail suspension test in mice
- Biology, MedicinePharmacology Biochemistry and Behavior
- 2022
Chapter 6 Association of 5-HT 1 A Receptors with Affective Disorders
- Biology, Psychology
- 2018
The purpose of this chapter is to analyze and discuss the current information about 5-HT 1A -R-mediated signaling cascades, the intracellular signaling of 5- HT 1A-R, in addition to their expression and pharmacology that are important to treatment of affective disorders symptoms.
References
SHOWING 1-10 OF 68 REFERENCES
EMD 68843, a serotonin reuptake inhibitor with selective presynaptic 5-HT1A receptor agonistic properties.
- Biology, ChemistryEuropean journal of pharmacology
- 1997
WAY100135: a novel, selective antagonist at presynaptic and postsynaptic 5-HT1A receptors.
- Biology, ChemistryEuropean journal of pharmacology
- 1993
Antidepressant-like behavioral effects in 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) receptor mutant mice.
- Biology, PsychologyThe Journal of pharmacology and experimental therapeutics
- 2001
The results suggest that 5-HT(1A) and 5- HT(1B) receptors have different roles in the modulation of the response to antidepressant drugs in the TST, suggesting mediation by enhanced catecholamine function.
Agonist-independent activation of Gz by the 5-hydroxytryptamine1A receptor co-expressed in Spodoptera frugiperda cells. Distinguishing inverse agonists from neutral antagonists.
- BiologyThe Journal of biological chemistry
- 1997
The human 5-hydroxytryptamine1A receptor, when expressed in Spodoptera frugiperda (Sf9) cells, facilitates the binding of [35S]GTPgammaS to a co-expressed GTP-binding regulatory protein, Gz, consistent with constitutive activity, using G protein activation as an index of receptor activity.
Idazoxan and 8-OH-DPAT Modify the Behavioral Effects Induced by Either NA, or 5-HT, or Dual NA/5-HT Reuptake Inhibition in the Rat Forced Swimming Test
- Biology, PsychologyNeuropsychopharmacology
- 2001
Postsynaptic 5-HT1A receptors mediate 5-hydroxytryptamine release in the amygdala through a feedback to the caudal linear raphe.
- BiologyEuropean journal of pharmacology
- 1997
Genetic regulation of extracellular serotonin by 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) autoreceptors in different brain regions of the mouse.
- Biology, ChemistryThe Journal of pharmacology and experimental therapeutics
- 2001
Results indicate common topographical regulation of 5-HT release in different brain regions by genetic mutation and pharmacological challenges and play a larger role in regulating 5- HT release in the striatum and possibly other brain regions innervated by the dorsal raphe nucleus.
Partial 5-HT1A receptor agonist properties of (–)pindolol in combination with citalopram on serotonergic dorsal raphe cell firing in vivo
- Biology, ChemistryPsychopharmacology
- 2000
The present findings support the previous notion that (–)pindolol possesses prominent agonistic activity at somatodendritic 5-HT1A autoreceptors, but also indicate that it may possess a weak antagonistic action at these receptors.
Effect of the 5-HT1A receptor agonist 8-OH-DPAT on the release of 5-HT in dorsal and median raphe-innervated rat brain regions as measured by in vivo microdialysis.
- BiologyLife sciences
- 1991
Effects of (−)‐tertatolol, (−)‐penbutolol and (±)‐pindolol in combination with paroxetine on presynaptic 5‐HT function: an in vivo microdialysis and electrophysiological study
- Biology, MedicineBritish journal of pharmacology
- 1999
The data suggest that (-)‐tertatolol and (−)‐penbutolol are superior to (±)‐pindolol in terms of enhancing the effect of an SSRI on extracellular 5‐HT in the frontal cortex and both are worthy of investigation for use as adjuncts to SSRIs in the treatment of major depression.