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Neurochemical evaluation of the novel 5-HT1A receptor partial agonist/serotonin reuptake inhibitor, vilazodone.
Eur J Pharmacol 2005; 510(1-2):49-57EJ

Abstract

Vilazodone has been reported to be an inhibitor of 5-hydoxytryptamine (5-HT) reuptake and a partial agonist at 5-HT1A receptors. Using [35S]GTPgammaS 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 [3H]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 8-OH-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-HT(1A) 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.

Authors+Show Affiliations

Neuropharmacology Research, Psychiatry CEDD, Glaxo Smith Kline, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15740724

Citation

Hughes, Zoë A., et al. "Neurochemical Evaluation of the Novel 5-HT1A Receptor Partial Agonist/serotonin Reuptake Inhibitor, Vilazodone." European Journal of Pharmacology, vol. 510, no. 1-2, 2005, pp. 49-57.
Hughes ZA, Starr KR, Langmead CJ, et al. Neurochemical evaluation of the novel 5-HT1A receptor partial agonist/serotonin reuptake inhibitor, vilazodone. Eur J Pharmacol. 2005;510(1-2):49-57.
Hughes, Z. A., Starr, K. R., Langmead, C. J., Hill, M., Bartoszyk, G. D., Hagan, J. J., ... Dawson, L. A. (2005). Neurochemical evaluation of the novel 5-HT1A receptor partial agonist/serotonin reuptake inhibitor, vilazodone. European Journal of Pharmacology, 510(1-2), pp. 49-57.
Hughes ZA, et al. Neurochemical Evaluation of the Novel 5-HT1A Receptor Partial Agonist/serotonin Reuptake Inhibitor, Vilazodone. Eur J Pharmacol. 2005 Mar 7;510(1-2):49-57. PubMed PMID: 15740724.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neurochemical evaluation of the novel 5-HT1A receptor partial agonist/serotonin reuptake inhibitor, vilazodone. AU - Hughes,Zoë A, AU - Starr,Kathryn R, AU - Langmead,Christopher J, AU - Hill,Matthew, AU - Bartoszyk,Gerd D, AU - Hagan,James J, AU - Middlemiss,Derek N, AU - Dawson,Lee A, PY - 2004/08/02/received PY - 2004/12/10/revised PY - 2005/01/13/accepted PY - 2005/3/3/pubmed PY - 2005/6/29/medline PY - 2005/3/3/entrez SP - 49 EP - 57 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 510 IS - 1-2 N2 - Vilazodone has been reported to be an inhibitor of 5-hydoxytryptamine (5-HT) reuptake and a partial agonist at 5-HT1A receptors. Using [35S]GTPgammaS 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 [3H]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 8-OH-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-HT(1A) 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. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/15740724/Neurochemical_evaluation_of_the_novel_5_HT1A_receptor_partial_agonist/serotonin_reuptake_inhibitor_vilazodone_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(05)00041-5 DB - PRIME DP - Unbound Medicine ER -