Characterization of Ro 04-6790 and Ro 63-0563: potent and selective antagonists at human and rat 5-HT6 receptors

British Journal of Pharmacology
Andrew J SleightA Bourson

Abstract

1. This study describes the in vitro characterization of two potent and selective 5-HT6 receptor antagonists at the rat and human recombinant 5-HT6 receptor. 2. In binding assays with [3H]-LSD, 4-amino-N-(2,6 bis-methylamino-pyrimidin-4-yl)-benzene sulphonamide (Ro 04-6790) and 4-amino-N-(2,6 bis-methylamino-pyridin-4-yl)-benzene sulphonamide (Ro 63-0563) had mean pKi values +/-s.e.mean at the rat 5-HT6 receptor of 7.35+/-0.04 and 7.83+/-0.01, respectively and pKi values at the human 5-HT6 receptor of 7.26+/-0.06 and 7.91+/-0.02, respectively. 3 .Both compounds were found to be over 100 fold selective for the 5-HT6 receptor compared to 23 (Ro 04-6790) and 69 (Ro 63-0563) other receptor binding sites. 4. In functional studies, neither compound had any significant effect on basal levels of cyclicAMP accumulation in Hela cells stably expressing the human 5-HT6 receptor, suggesting that the compounds are neither agonists nor inverse agonists at the 5-HT6 receptor. However, both Ro 04-6790 and Ro 63-0563 behaved as competitive antagonists with mean +/-s.e.mean pA2 values of 6.75+/-0.07 and 7.10+/-0.09, respectively. 5. In rats habituated to observation cages, Ro 04-6790 produced a behavioural syndrome similar to that seen following ...Continue Reading

References

Mar 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·J MacDermotM Nirenberg
Nov 1, 1985·Journal of Pharmacological Methods·G A McPherson
Sep 1, 1980·Analytical Biochemistry·P J Munson, D Rodbard
Nov 1, 1994·Synapse·S J Peroutka
Mar 1, 1994·Neuropharmacology·F G Boess, I L Martin
May 28, 1993·Biochemical and Biophysical Research Communications·M RuatJ C Schwartz
Mar 1, 1959·British Journal of Pharmacology and Chemotherapy·O ARUNLAKSHANA, H O SCHILD

❮ Previous
Next ❯

Citations

Mar 31, 2004·Bioorganic & Medicinal Chemistry Letters·Jean Chang-FongRichard A Glennon
Jul 16, 2008·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Neil UptonDavid J Virley
Dec 4, 2003·Progress in Neuro-psychopharmacology & Biological Psychiatry·Herbert Y MeltzerJunji Ichikawa
Jul 16, 2003·European Journal of Pharmacology·Jean Y ZhangJohn Dunlop
Aug 26, 1999·Neuropharmacology·N M Barnes, T Sharp
Mar 13, 2002·Pharmacology, Biochemistry, and Behavior·B PouzetJ Arnt
Mar 13, 2002·Pharmacology, Biochemistry, and Behavior·Daniel HoyerGraeme R Martin
Jan 22, 2000·Neuroscience and Biobehavioral Reviews·A Meneses
Jun 15, 1999·Trends in Pharmacological Sciences·D L MurphyA Heils
Oct 31, 2000·Bioorganic & Medicinal Chemistry Letters·Y TsaiR A Glennon
Sep 3, 2003·Bioorganic & Medicinal Chemistry Letters·Manik R PullagurlaRichard A Glennon
Jan 12, 1999·British Journal of Pharmacology·A BoursonA J Sleight
Aug 6, 2000·British Journal of Pharmacology·C RoutledgeD N Middlemiss
Feb 3, 2006·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Stephen J BonaseraLaurence H Tecott
Feb 3, 1999·Annals of the New York Academy of Sciences·A J SleightA Bourson
Jan 16, 2009·Molecular Interventions·Irina Zabbarova, Anthony Kanai
Jun 3, 2000·Annual Review of Pharmacology and Toxicology·T A Branchek, T P Blackburn
Apr 2, 2002·Expert Opinion on Investigational Drugs·Martyn D WoodJeannette M Watson
Nov 18, 2015·Journal of Computer-aided Molecular Design·Márton VassÁkos Tarcsay
Dec 26, 2006·Journal of Pharmacological and Toxicological Methods·Stanley P NawoschikXavier Khawaja
Jun 14, 2006·Journal of Pharmacological and Toxicological Methods·Gonzalo RomeroPetrus J Pauwels
Oct 27, 2004·Pharmacology & Therapeutics·Takafumi NagatomoTadazumi Komiyama
Oct 6, 2005·Journal of Psychopharmacology·John C TalposTrevor W Robbins
Jul 12, 2005·Pharmacology & Therapeutics·Ellen S Mitchell, John F Neumaier
May 9, 2007·Bioorganic & Medicinal Chemistry Letters·Shu-Hai ZhaoLudmila Alexandrova
Aug 2, 2005·Bioorganic & Medicinal Chemistry Letters·Cecilia MattssonHenning Böttcher

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.