+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

In vitro profile of the antidepressant candidate OPC-14523 at rat and human 5-HT1A receptors



In vitro profile of the antidepressant candidate OPC-14523 at rat and human 5-HT1A receptors



European Journal of Pharmacology 517(3): 165-173



This study determined the in vitro functional profile of 1-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-5-methoxy-3,4-dihydro-2-quinolinone monomethanesulfonate (OPC-14523) at rat and human serotonin (5-HT) 5-HT1A receptors and binding affinity of OPC-14523 at human frontocortical 5-HT1A receptors. OPC-14523 (1 microM) increased guanosine-5'-O-(3-[35S]thio)-triphosphate ([35S]GTPgammaS) binding to 5-HT1A receptor-containing regions of rat brain tissue sections (approximately 53% of the effect of 1 microM (+)8-hydroxy-2-(di-n-propylamino)tetralin ((+)8-OH-DPAT) that were blocked by the selective 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY-100635). OPC-14523 also behaved as a partial agonist in its stimulation of [35S]GTPgammaS binding to membranes from rat hippocampus (pEC50=7.60+/-0.23, Emax=41.1% of the effect of 10 microM (+)8-OH-DPAT), human frontal cortex (pEC50=7.89+/-0.08; Emax=64% of the effect of 10 microM (+)8-OH-DPAT), and Chinese Hamster Ovary cells expressing cloned human 5-HT1A receptors (pEC50=8.0+/-0.11; Emax=85.5% of the effect of 10 microM 5-HT), and all of these effects of OPC-14523 were blocked by WAY-100635. Taken together, these data support the development of OPC-14523 as an antidepressant whose mechanism of action involves potent partial agonist activity at 5-HT1A receptors.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 012193059

Download citation: RISBibTeXText

PMID: 15985260

DOI: 10.1016/j.ejphar.2005.05.035


Related references

The antidepressant drug candidate OPC-14523 is a partial agonist at rat and recombinant human 5-HT1A receptors. Society for Neuroscience Abstracts 26(1-2): Abstract No -387 13, 2000

Effects of OPC-14523, a combined sigma and 5-HT1a ligand, on pre- and post-synaptic 5-HT1a receptors. Journal of Psychopharmacology 21(1): 85-92, 2007

Antidepressant-like responses to the combined sigma and 5-HT1A receptor agonist OPC-14523. Neuropharmacology 41(8): 976-988, 2001

Pharmacological profile of OPC-14523 A novel sigma and 5-HT1A receptor agonist. Japanese Journal of Pharmacology 71(Suppl. 1): 271P, 1996

Effects of the potential antidepressant OPC-14523 -1-piperazinylpropyl-5-methoxy-3,4-dihydro-2-quinolinone monomethanesulfonate a combined sigma and 5-HT1A ligand Modulation of neuronal activity in the dorsal raphe nucleus. Journal of Pharmacology & Experimental Therapeutics 310(2): 578-583, 2004

Role for sigma and 5-HT1A receptors in the forced swimming test supporting the mechanism of action of OPC-14523. Society for Neuroscience Abstracts 26(1-2): Abstract No -871 7, 2000

Effects of the potential antidepressant OPC-14523 [1-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-5-methoxy-3,4-dihydro-2-quinolinone monomethanesulfonate] a combined sigma and 5-HT1A ligand: modulation of neuronal activity in the dorsal raphe nucleus. Journal of Pharmacology and Experimental Therapeutics 310(2): 578-583, 2004

Effects of the potential antidepressant OPC-14523 (1-(3-(4-(3-chlorophenyl)-1-piperazinyl)propyl)-5-methoxy-3,4-dihydro-2-quinolinone monomethanesulfonate) a combined sigma and 5-HT1A ligand: Modulation of neuronal activity in the dorsal raphe nucleus. Journal of Pharmacology and Experimental Therapeutics 310(2): 578-583, 2004

In vitro profile of Lu 36 - 274 a compound with combined 5 - HTt/5 - HT1A activity and putative fast onset of antidepressant action. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 958 16, 2003

Blockade of 5-HT1A receptors by (+/-)-pindolol potentiates cortical 5-HT outflow, but not antidepressant-like activity of paroxetine: microdialysis and behavioral approaches in 5-HT1A receptor knockout mice. Neuropsychopharmacology 31(10): 2162-2172, 2006

S 15535, a novel benzodioxopiperazine ligand of serotonin (5-HT)1A receptors: I. Interaction with cloned human (h)5-HT1A, dopamine hD2/hD3 and h alpha2A-adrenergic receptors in relation to modulation of cortical monoamine release and activity in models of potential antidepressant activity. Journal of Pharmacology and Experimental Therapeutics 282(1): 132-147, 1997

Effect of triiodothyronine on antidepressant screening tests in mice and on presynaptic 5-HT1A receptors: mediation by thyroid hormone α receptors. Journal of Pharmacology and Experimental Therapeutics 337(2): 494-502, 2011

Effect of Triiodothyronine on Antidepressant Screening Tests in Mice and on Presynaptic 5-HT1A Receptors Mediation by Thyroid Hormone alpha Receptors. 2011

The novel antidepressant agomelatine acts independently of 5-HT1A receptors in the rat. European Neuropsychopharmacology 13(Suppl. 4): S237, 2003