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Neurochemical evaluation of the novel 5-HT1A receptor partial agonist/serotonin reuptake inhibitor, vilazodone
- Source :
- European Journal of Pharmacology. 510:49-57
- Publication Year :
- 2005
- Publisher :
- Elsevier BV, 2005.
-
Abstract
- Vilazodone has been reported to be an inhibitor of 5-hydoxytryptamine (5-HT) reuptake and a partial agonist at 5-HT1A receptors. Using [ 35 S]GTPgS binding in rat hippocampal tissue, vilazodone was demonstrated to have an intrinsic activity comparable to the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Vilazodone (1–10 mg/kg p.o.) dose-dependently displaced in vivo [ 3 H]DASB (N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine) binding from rat cortex and hippocampus, indicating that vilazodone occupies 5-HT transporters in vivo. Using in vivo microdialysis, vilazodone (10 mg/kg p.o.) was demonstrated to cause a 2-fold increase in extracellular 5-HT but no change in noradrenaline or dopamine levels in frontal cortex of freely moving rats. In contrast, administration of 8OH-DPAT (0.3 mg/kg s.c.), either alone or in combination with a serotonin specific reuptake inhibitor (SSRI; paroxetine, 3 mg/kg p.o.), produced no increase in cortical 5-HT whilst increasing noradrenaline and dopamine 2 and 4 fold, respectively. A 2-fold increase in extracellular 5-HT levels (but no change in noradrenaline or dopamine levels) was observed after combination of the 5-HT1A receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(pyridinyl)cyclohexanecarboxamide) (WAY-100635; 0.3 mg/kg s.c.) and paroxetine (3 mg/kg p.o.). In summary, vilazodone behaved as a high efficacy partial agonist at the rat hippocampal 5-HT1A receptors in vitro and occupied 5-HT transporters in vivo. In vivo vilazodone induced a selective increase in extracellular levels of 5-HT in the rat frontal cortex. This profile was similar to that seen with a 5-HT1A receptor antagonist plus an SSRI but in contrast to 8-OH-DPAT either alone or in combination with paroxetine. D 2005 Elsevier B.V. All rights reserved.
- Subjects :
- Male
Agonist
Benzylamines
Serotonin
Indoles
Time Factors
Pyridines
medicine.drug_class
Dopamine
Microdialysis
Serotonin reuptake inhibitor
Vilazodone Hydrochloride
Pharmacology
Sulfur Radioisotopes
Tritium
Binding, Competitive
Hippocampus
Partial agonist
Piperazines
Reuptake
Rats, Sprague-Dawley
Norepinephrine
chemistry.chemical_compound
Vilazodone
medicine
Animals
Spiro Compounds
Piperidones
Benzofurans
8-Hydroxy-2-(di-n-propylamino)tetralin
Dose-Response Relationship, Drug
Chemistry
Cell Membrane
Serotonin 5-HT1 Receptor Agonists
Receptor antagonist
Frontal Lobe
Rats
Serotonin Receptor Agonists
Paroxetine
Guanosine 5'-O-(3-Thiotriphosphate)
5-HT1A receptor
Serotonin Antagonists
Extracellular Space
Selective Serotonin Reuptake Inhibitors
Subjects
Details
- ISSN :
- 00142999
- Volume :
- 510
- Database :
- OpenAIRE
- Journal :
- European Journal of Pharmacology
- Accession number :
- edsair.doi.dedup.....f7e20b4792a186cb9661a5447b636a9f