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In vitro profile of the antidepressant candidate OPC-14523 at rat and human 5-HT1A receptors.
Eur J Pharmacol. 2005 Jul 11; 517(3):165-73.EJ

Abstract

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.

Authors+Show Affiliations

Department of Neuroscience Research, Otsuka Maryland Medicinal Laboratories, 9900 Medical Center Drive, Rockville, MD 20850, USA. shaunj@otsuka.comNo 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
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15985260

Citation

Jordan, Shaun, et al. "In Vitro Profile of the Antidepressant Candidate OPC-14523 at Rat and Human 5-HT1A Receptors." European Journal of Pharmacology, vol. 517, no. 3, 2005, pp. 165-73.
Jordan S, Chen R, Koprivica V, et al. In vitro profile of the antidepressant candidate OPC-14523 at rat and human 5-HT1A receptors. Eur J Pharmacol. 2005;517(3):165-73.
Jordan, S., Chen, R., Koprivica, V., Hamilton, R., Whitehead, R. E., Tottori, K., & Kikuchi, T. (2005). In vitro profile of the antidepressant candidate OPC-14523 at rat and human 5-HT1A receptors. European Journal of Pharmacology, 517(3), 165-73.
Jordan S, et al. In Vitro Profile of the Antidepressant Candidate OPC-14523 at Rat and Human 5-HT1A Receptors. Eur J Pharmacol. 2005 Jul 11;517(3):165-73. PubMed PMID: 15985260.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro profile of the antidepressant candidate OPC-14523 at rat and human 5-HT1A receptors. AU - Jordan,Shaun, AU - Chen,Ruoyan, AU - Koprivica,Vuk, AU - Hamilton,Ronald, AU - Whitehead,Richard E, AU - Tottori,Katsura, AU - Kikuchi,Tetsuro, PY - 2005/05/20/received PY - 2005/05/24/accepted PY - 2005/6/30/pubmed PY - 2005/9/13/medline PY - 2005/6/30/entrez SP - 165 EP - 73 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 517 IS - 3 N2 - 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. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/15985260/In_vitro_profile_of_the_antidepressant_candidate_OPC_14523_at_rat_and_human_5_HT1A_receptors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(05)00569-8 DB - PRIME DP - Unbound Medicine ER -