Effects of the brain-penetrant and selective 5-HT6 receptor antagonist SB-399885 in animal models of anxiety and depression
- PMID: 17320917
- DOI: 10.1016/j.neuropharm.2007.01.007
Effects of the brain-penetrant and selective 5-HT6 receptor antagonist SB-399885 in animal models of anxiety and depression
Abstract
The effects of a selective 5-HT(6) receptor antagonist, SB-399885 (N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)benzenesulfonamide), were evaluated in behavioural tests sensitive to clinically effective anxiolytic- and antidepressant-compounds using diazepam and imipramine as reference drugs. In the Vogel conflict drinking test in rats, SB-399885 (1-3mg/kg i.p.) caused an anxiolytic-like activity comparable to that of diazepam (2.5-5mg/kg i.p.). An anxiolytic-like effect was also seen in the elevated plus-maze test in rats, where SB-399885 (0.3-3mg/kg i.p.) was slightly weaker than diazepam (2.5-5mg/kg i.p.). In the four-plate test in mice, SB-399885 (3-20mg/kg i.p.) showed an anxiolytic-like effect which was weaker than that produced by diazepam (2.5-5mg/kg i.p.). In the forced swim test in rats, SB-399885 (10mg/kg i.p.) significantly shortened the immobility time and the effect was stronger than that of imipramine (30mg/kg i.p.). In the forced swim test in mice, SB-399885 (20-30mg/kg i.p.) had an anti-immobility action, comparable to imipramine (30mg/kg i.p.) and also in the tail suspension test in mice, SB-399885 (10-30mg/kg i.p.) had an antidepressant-like effect, though was weaker than imipramine (10-20mg/kg i.p.). The tested 5-HT(6) antagonist (3-20mg/kg i.p.) shortened the walking time of rats in the open field test and, at a dose of 30mg/kg i.p. reduced the locomotor activity of mice. SB-399885 (in doses up to 30mg/kg i.p.) did not affect motor coordination in mice and rats tested in the rota-rod test. Such data indicate that the selective 5-HT(6) receptor antagonist SB-399885had specific effects, indicative of this compound's anxiolytic and antidepressant potential.
Similar articles
-
Effect of the selective 5-HT7 receptor antagonist SB 269970 in animal models of anxiety and depression.Neuropharmacology. 2006 Sep;51(3):578-86. doi: 10.1016/j.neuropharm.2006.04.017. Epub 2006 Jul 7. Neuropharmacology. 2006. PMID: 16828124
-
Anxiolytic-like and antidepressant-like effects produced by the selective 5-HT6 receptor antagonist SB-258585 after intrahippocampal administration to rats.Behav Pharmacol. 2007 Sep;18(5-6):439-46. doi: 10.1097/FBP.0b013e3282d28f9c. Behav Pharmacol. 2007. PMID: 17762512
-
Potential anxiolytic and antidepressant effects of the selective 5-HT7 receptor antagonist SB 269970 after intrahippocampal administration to rats.Eur J Pharmacol. 2006 Dec 28;553(1-3):185-90. doi: 10.1016/j.ejphar.2006.09.064. Epub 2006 Oct 10. Eur J Pharmacol. 2006. PMID: 17097082
-
Potential role of the 5-HT6 receptor in depression and anxiety: an overview of preclinical data.Pharmacol Rep. 2010 Jul-Aug;62(4):564-77. doi: 10.1016/s1734-1140(10)70315-7. Pharmacol Rep. 2010. PMID: 20884998 Review.
-
Ameliorating effects of aripiprazole on cognitive functions and depressive-like behavior in a genetic rat model of absence epilepsy and mild-depression comorbidity.Neuropharmacology. 2013 Jan;64:371-9. doi: 10.1016/j.neuropharm.2012.06.039. Epub 2012 Jul 2. Neuropharmacology. 2013. PMID: 22766393 Review.
Cited by
-
Potential Anti-Amnesic Activity of a Novel Multimodal Derivative of Salicylamide, JJGW08, in Mice.Pharmaceuticals (Basel). 2023 Mar 6;16(3):399. doi: 10.3390/ph16030399. Pharmaceuticals (Basel). 2023. PMID: 36986498 Free PMC article.
-
Leucine-Rich Repeats and Transmembrane Domain 2 Controls Protein Sorting in the Striatal Projection System and Its Deficiency Causes Disturbances in Motor Responses and Monoamine Dynamics.Front Mol Neurosci. 2022 May 9;15:856315. doi: 10.3389/fnmol.2022.856315. eCollection 2022. Front Mol Neurosci. 2022. PMID: 35615067 Free PMC article.
-
Rewiring of the Serotonin System in Major Depression.Front Psychiatry. 2021 Dec 16;12:802581. doi: 10.3389/fpsyt.2021.802581. eCollection 2021. Front Psychiatry. 2021. PMID: 34975594 Free PMC article. Review.
-
Structure-Based Design and Optimization of FPPQ, a Dual-Acting 5-HT3 and 5-HT6 Receptor Antagonist with Antipsychotic and Procognitive Properties.J Med Chem. 2021 Sep 23;64(18):13279-13298. doi: 10.1021/acs.jmedchem.1c00224. Epub 2021 Sep 1. J Med Chem. 2021. PMID: 34467765 Free PMC article.
-
5-HT Receptors and the Development of New Antidepressants.Int J Mol Sci. 2021 Aug 20;22(16):9015. doi: 10.3390/ijms22169015. Int J Mol Sci. 2021. PMID: 34445721 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical