SB-399885

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H21Cl2N3O4S
Molecular Weight	446.348
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=C(C=C(C=C1)S(=O)(=O)NC2=CC(Cl)=CC(Cl)=C2OC)N3CCNCC3

InChI

InChIKey=ATKZKAYWARYLBW-UHFFFAOYSA-N

InChI=1S/C18H21Cl2N3O4S/c1-26-17-4-3-13(11-16(17)23-7-5-21-6-8-23)28(24,25)22-15-10-12(19)9-14(20)18(15)27-2/h3-4,9-11,21-22H,5-8H2,1-2H3

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17069795
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20732355 | https://www.ncbi.nlm.nih.gov/pubmed/17320917 | https://www.ncbi.nlm.nih.gov/pubmed/19422883 | https://www.ncbi.nlm.nih.gov/pubmed/25034463

is a potent, selective, brain penetrant, orally active serotonin 5-HT(6) receptor antagonist with cognitive enhancing, anxiolytic and antidepressant properties. It is able to regulate sleep and wakefulness in rodents. In addition it demostrates antinociceptive and antiepileptic potentials.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serotonin 6 (5-HT6) receptor 45 Target ID: CHEMBL3371 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17069795	Antagonist 2778		9.11 null [pKi]

Conditions

Condition	Modality	Highest Phase	Product
Depression 235 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24905514 https://www.ncbi.nlm.nih.gov/pubmed/25863120 https://www.ncbi.nlm.nih.gov/pubmed/18195455 https://www.ncbi.nlm.nih.gov/pubmed/18234190 https://www.ncbi.nlm.nih.gov/pubmed/19302808 https://www.ncbi.nlm.nih.gov/pubmed/17320917	Primary	Preclinical	Unknown Approved Use Unknown
Anxiety 267 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18096153 https://www.ncbi.nlm.nih.gov/pubmed/17320917	Primary	Preclinical	Unknown Approved Use Unknown
Cognition disorders 21 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19733250 https://www.ncbi.nlm.nih.gov/pubmed/15964617 https://www.ncbi.nlm.nih.gov/pubmed/15846482 https://www.ncbi.nlm.nih.gov/pubmed/17069795	Primary	Preclinical	Unknown Approved Use Unknown
Pain 614 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19422883	Primary	Preclinical	Unknown Approved Use Unknown
Epilepsy 121 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25034463	Primary	Preclinical	Unknown Approved Use Unknown
Traumatic stress disorder 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25310249	Primary	Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Oral administration of the 5-HT6 receptor antagonists SB-357134 and SB-399885 improves memory formation in an autoshaping learning task.	2005 Jul	15964617
SB-399885 is a potent, selective 5-HT6 receptor antagonist with cognitive enhancing properties in aged rat water maze and novel object recognition models.	2006 Dec 28	17069795
Effects of the brain-penetrant and selective 5-HT6 receptor antagonist SB-399885 in animal models of anxiety and depression.	2007 Apr	17320917
5-HT6 receptor antagonist SB-399885 potentiates haloperidol and risperidone-induced dopamine efflux in the medial prefrontal cortex or hippocampus.	2007 Feb 23	17207474
Memory consolidation and amnesia modify 5-HT6 receptors expression in rat brain: an autoradiographic study.	2007 Mar 12	17267053
Role of 5-HT1-7 receptors in short- and long-term memory for an autoshaping task: intrahippocampal manipulations.	2007 May 25	17368430
Study into a possible mechanism responsible for the antidepressant-like activity of the selective 5-HT6 receptor antagonist SB-399885 in rats.	2007 Nov-Dec	18195455
Effects of 5-HT drugs in prefrontal cortex during memory formation and the ketamine amnesia-model.	2008	18570192
The effects of the 5-HT(6) receptor agonist EMD and the 5-HT(7) receptor agonist AS19 on memory formation.	2008 Dec 16	18191236
The anxiolytic-like effect of the selective 5-HT6 receptor antagonist SB-399885: the impact of benzodiazepine receptors.	2008 Feb 12	18096153
The selective 5-HT6 receptor antagonists SB-271046 and SB-399885 potentiate NCAM PSA immunolabeling of dentate granule cells, but not neurogenesis, in the hippocampal formation of mature Wistar rats.	2008 Jun	18455201
The selective 5-HT(6) receptor antagonist SB-399885 enhances anti-immobility action of antidepressants in rats.	2008 Mar 17	18234190
Procognitive 5-HT6 antagonists in the rat forced swimming test: potential therapeutic utility in mood disorders associated with Alzheimer's disease.	2009 Apr 10	19302808
Role of peripheral and spinal 5-HT6 receptors according to the rat formalin test.	2009 Aug 18	19422883
Activation of the 5-HT(6) receptor attenuates long-term potentiation and facilitates GABAergic neurotransmission in rat hippocampus.	2009 Dec 1	19660530
Dimebolin is a 5-HT6 antagonist with acute cognition enhancing activities.	2009 Oct 15	19549510
Time-course of 5-HT(6) receptor mRNA expression during memory consolidation and amnesia.	2010 Jan	19733250
Activation of 5-HT(6) receptors facilitates attentional set shifting.	2010 Jan	19902184
Effects of the 5-HT₆ receptor antagonists SB-399885 and RO-4368554 and of the 5-HT(2A) receptor antagonist EMD 281014 on sleep and wakefulness in the rat during both phases of the light-dark cycle.	2011 Jan 1	20732355
The 5-HT6 receptor agonist EMD 386088 produces antidepressant and anxiolytic effects in rats after intrahippocampal administration.	2011 Oct	21499701
Synthesis and in vivo evaluation of [O-methyl-11C] N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)benzenesulfonamide as an imaging probe for 5-HT6 receptors.	2011 Sep 1	21821420
Co-administration of 5-HT6 receptor antagonists with clozapine, risperidone, and a 5-HT2A receptor antagonist: effects on prepulse inhibition in rats.	2014 Jan	23954911
Role of glutamate and advantages of combining memantine with a 5HT6 ligand in a model of depression.	2014 Jun	24905514
Distribution of cells responsive to 5-HT₆ receptor antagonist-induced hypophagia.	2014 Jun 1	24566060
5-HT6 Receptor Recruitment of mTOR Modulates Seizure Activity in Epilepsy.	2015	25034463
GR-127935-sensitive mechanism mediating hypotension in anesthetized rats: are 5-HT5B receptors involved?	2015 Apr	25502305
Therapeutic Potential of 5-HT6 Antagonist SB399885 in Traumatic Stress Disorder.	2015 Aug	25310249
Olanzapine augments the effect of selective serotonin reuptake inhibitors by suppressing GABAergic inhibition via antagonism of 5-HT₆ receptors in the dorsal raphe nucleus.	2015 Aug	25863120
Pharmacological Evidence for 5-HT6 Receptor Modulation of 5-HT Neuron Firing in Vivo.	2015 Jul 15	25837696
5-HT6 Receptor Agonist and Antagonist Against β-Amyloid-Peptide-Induced Neurotoxicity in PC-12 Cells.	2017 May	28271324

Patents

Sample Use Guides

In Vivo Use Guide

rats: 10 mg/kg p.o., b.i.d. for 7 days rats: 1 and 3 mg/kg, i.p.

Route of Administration: Other

In Vitro Use Guide

As assessed by measuring and evaluating spontaneous inhibitory postsynaptic currents (sIPSCs) in the rat brain slices containing area CA1 of the hippocampus, 200 nM WAY-181187, the selective 5-HT(6) agonist, increased sIPSC frequency, this increase in GABA sIPSCs was prevented by the selective 5-HT(6) antagonist SB-399885 (300 nM).

Name

Type

Language

SB-399885

Common Name

English

N-(3,5-DICHLORO-2-METHOXYPHENYL)-4-METHOXY-3-(1-PIPERAZINYL)BENZENESULFONAMIDE

Systematic Name

English

BENZENESULFONAMIDE, N-(3,5-DICHLORO-2-METHOXYPHENYL)-4-METHOXY-3-(1-PIPERAZINYL)-

Systematic Name

English

SB399885

Code

English

Code System Code Type Description

PUBCHEM

6918649