Home>>Signaling Pathways>> Neuroscience>> 5-HT Receptor>>SB-242084 (hydrochloride)

SB-242084 (hydrochloride) Sale

(Synonyms: 6-氯-2,3-二氢-5-甲基-N-[6-[(2-甲基-3-吡啶基)氧]-3-吡啶基]-1H-吲哚-1-酰胺盐酸盐) 目录号 : GC44875

Specific antagonist of 5-HT2C

SB-242084 (hydrochloride) Chemical Structure

Cas No.:1049747-87-6

规格 价格 库存 购买数量
1mg
¥515.00
现货
5mg
¥990.00
现货
10mg
¥1,287.00
现货

电话:400-920-5774 Email: sales@glpbio.cn

Customer Reviews

Based on customer reviews.

Sample solution is provided at 25 µL, 10mM.

产品文档

Quality Control & SDS

View current batch:

产品描述

SB 242084 hydrochloride is a 5-HT2C receptor antagonist(pKi=9.0) that displays 158- and 100-fold selectivity over 5-HT2A and 5-HT2B receptors respectively.IC50 value: 9.0(pKi) [1]Target: 5-HT2C antagonistin vitro: SB 242084 had over 100-fold selectivity over a range of other 5-HT, dopamine and adrenergic receptors. In studies of 5-HT-stimulated phosphatidylinositol hydrolysis using SH-SY5Y cells stably expressing the cloned human 5-HT2C receptor, SB 242084 acted as an antagonist with a pKb of 9.3, which closely resembled its corresponding receptor binding affinity [1].in vivo: SB 242084 potently inhibited m-chlorophenylpiperazine (mCPP, 7 mgkg i.p. 20 min pre-test)-induced hypolocomotion in rats, a model of in vivo central 5-HT2C receptor function, with an ID50 of 0.11 mg/kg i.p., and 2.0 mg/kg p.o. SB 242084 (0.1-1 mg/kg i.p.) exhibited an anxiolytic-like profile in the rat social interaction test, increasing time spent in social interaction, but having no effect on locomotion. SB 242084 (0.1-1 mg/kg i.p.) also markedly increased punished responding in a rat Geller-Seifter conflict test of anxiety, but had no consistent effect on unpunished responding [1].

References:
[1]. Kennett GA, et al. SB 242084, a selective and brain penetrant 5-HT2C receptor antagonist. Neuropharmacology. 1997 Apr-May;36(4-5):609-20.
[2]. Bromidge SM, et al. 6-Chloro-5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]- indoline (SB-242084): the first selective and brain penetrant 5-HT2C receptor antagonist. J Med Chem. 1997 Oct 24;40(22):3494-6.
[3]. Dalton GL, et al. Serotonin 1B and 2C receptor interactions in the modulation of feeding behaviour in the mouse. Psychopharmacology (Berl). 2006 Mar;185(1):45-57.

Chemical Properties

Cas No. 1049747-87-6 SDF
别名 6-氯-2,3-二氢-5-甲基-N-[6-[(2-甲基-3-吡啶基)氧]-3-吡啶基]-1H-吲哚-1-酰胺盐酸盐
Canonical SMILES CC1=NC=CC=C1OC(N=C2)=CC=C2NC(N3CCC4=C3C=C(Cl)C(C)=C4)=O.Cl.Cl
分子式 C21H19ClN4O2•2HCl 分子量 467.8
溶解度 DMF: 30 mg/ml,DMSO: 30 mg/ml,Ethanol: 1 mg/ml,PBS (pH 7.2): 10 mg/ml 储存条件 Store at -20°C
General tips 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。
储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。
为了提高溶解度,请将管子加热至37℃,然后在超声波浴中震荡一段时间。
Shipping Condition 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。

溶解性数据

制备储备液
1 mg 5 mg 10 mg
1 mM 2.1377 mL 10.6883 mL 21.3767 mL
5 mM 0.4275 mL 2.1377 mL 4.2753 mL
10 mM 0.2138 mL 1.0688 mL 2.1377 mL
  • 摩尔浓度计算器

  • 稀释计算器

  • 分子量计算器

质量
=
浓度
x
体积
x
分子量
 
 
 
*在配置溶液时,请务必参考产品标签上、MSDS / COA(可在Glpbio的产品页面获得)批次特异的分子量使用本工具。

计算

动物体内配方计算器 (澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)
给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 ul 动物数量
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系GLPBIO为您提供正确的澄清溶液配方)
% DMSO % % Tween 80 % saline
计算重置

Research Update

Contrasting effects of DOI and lisuride on impulsive decision-making in delay discounting task

Psychopharmacology (Berl) 2022 Nov;239(11):3551-3565.PMID:36107207DOI:10.1007/s00213-022-06229-y.

Rationale: The 5-HT2A receptor is the major target of classic hallucinogens. Both DOI (2,5-dimethoxy-4-iodoamphetamine) and lisuride act at 5-HT2A receptors, and lisuride shares comparable affinity with DOI and acts as a partial agonist at 5-HT2A receptors. However, not like DOI, lisuride lacks hallucinogenic properties. Impulsive decision-making refers to the preference for an immediate small reinforcer (SR) over a delayed large reinforcer (LR). Objectives: The current study aims to compare the effects of DOI and lisuride on impulsive decision-making and further to investigate the possible receptor mechanisms responsible for the actions of the two drugs. Methods: Impulsive decision-making was evaluated in male Sprague-Dawley rats by the percentage of choice for the LR in delay discounting task (DDT). Delay to the LR changed in an ascending order (0, 4, 8, 16, and 32 s) across one session. Results: DOI (0.5 and 1.0 mg/kg) increased impulsive decision-making, and the effects of DOI (1.0 mg/kg) were blocked by the 5-HT2A receptor antagonist ketanserin (1.0 mg/kg) rather than the 5-HT2C receptor antagonist SB-242084 (1.0 mg/kg). Contrarily, lisuride (0.1, 0.3, and 0.5 mg/kg) decreased impulsive decision-making. The effects of lisuride (0.3 mg/kg) were not antagonized by ketanserin (1.0 mg/kg), selective 5-HT1A antagonist WAY-100635 (1.0 mg/kg), or selective dopamine D4 receptor antagonist L-745870 (1.0 mg/kg) but were attenuated by the selective dopamine D2/D3 receptor antagonist tiapride (40 mg/kg). Conclusions: DOI and lisuride have contrasting effects on impulsive decision-making via distinct receptors. DOI-induced increase of impulsivity is mediated by the 5-HT2A receptor, while lisuride-induced inhibition of impulsivity is regulated by the dopamine D2/D3 receptor.

Constitutive activity of the serotonin2C receptor inhibits in vivo dopamine release in the rat striatum and nucleus accumbens

J Neurosci 2004 Mar 31;24(13):3235-41.PMID:15056702DOI:10.1523/JNEUROSCI.0112-04.2004.

Numerous research has pointed out that serotonin2c (5-HT2C) receptor, a subtype of 5-HT receptors belonging to the G-protein-coupled receptor superfamily, modulates the activity of mesencephalic dopamine (DA) neurons, the dysfunction of which is involved in devastating diseases such as schizophrenia, Parkinson's disease, and drug addiction. In the present study, using in vivo intracerebral microdialysis and Chinese hamster ovary (CHO) cells expressing 5-HT2C receptors to identify appropriate 5-HT2C receptor ligands, we sought to determine whether the property of 5-HT2C receptors to spontaneously activate intracellular signaling pathways in vitro (constitutive activity) participates in the tonic inhibitory control that they exert on DA release in the rat striatum and nucleus accumbens in vivo. In CHO cells, the purported antagonist 5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f] indole hydrochloride (SB 206553), but not 6-chloro-5-methyl-1-[6-(2-methylpiridin-3-yloxy)pyridin-3-yl carbamoyl] indoline (SB 242084), decreased basal inositol phosphate accumulation, thus behaving as a 5-HT2C inverse agonist. Its effect was prevented by SB 242084. In vivo, SB 206553 (1-10 mg/kg) elicited a dose-dependent and clear-cut increase in accumbal and striatal DA release compared with SB 242084 (1-10 mg/kg), and the 5-HT2C agonist S-2-(6-chloro-5-fluoroindol-1-yl)-1-methylethylamine hydrochloride (Ro-60-0175) (0.3-3 mg/kg) inhibited DA release. Pretreatment by SB 242084 reversed the change in DA release elicited by Ro-60-0175 and SB 206553. Furthermore, SB 206553-stimulated DA release was insensitive to reduction of 5-HT neuronal function induced by the 5-HT1A agonist (+/-)-8-hydroxy-2-dipropylaminotetralin or intra-raphe injections of 5,7-dihydroxytryptamine neurotoxin. The obtained results provide the first in vivo evidence that constitutive activity of the 5-HT2C receptor tonically inhibits mesencephalic DA neurons and underscore the need for a better understanding of the pathophysiological role of constitutive receptor activity.

Regulation of septo-hippocampal activity by 5-hydroxytryptamine(2C) receptors

J Pharmacol Exp Ther 2003 Aug;306(2):605-15.PMID:12734389DOI:10.1124/jpet.103.051169.

It is established that the serotonin system modulates hippocampal functions by regulating neuronal activity of both the medial septum and hippocampus. Inhibition of serotonin neurons leads to theta oscillation of septal neurons and theta wave activity in the hippocampus, indicating a tonic regulation of the septo-hippocampal system by serotonin neurons. Because the postsynaptic 5-hydroxytryptamine (5-HT) receptor subtypes mediating this tonic inhibition have not been identified, a putative role of 5-HT2C receptors has been evaluated in the present study. Extracellular single units were recorded from the medial septum/vertical limb of diagonal band (MS/DBv) and hippocampal CA1 or dentate gyrus with simultaneous hippocampal EEG recordings from anesthetized rats. Intravenous administration of 5-HT2C receptor agonists 1-(3-chlorophenyl)piperazine dihydrochloride (m-CPP) and [S]-2-(chloro-5-fluoro-indol-1-yl)-1-methyl-ethylamine fumarate (Ro 60-0175) dose dependently inhibited firing activity most of the recorded MS/DBv neurons and abolished theta oscillation in all tested MS/DBv and hippocampal neurons. Parallel to inhibition of theta oscillation of MS/DBv neurons, hippocampal EEG activity was desynchronized and its power spectrum was shifted to lower frequencies. The selective 5-HT2C receptor antagonist 6-chloro-5-methyl-1-[2-(2-methylpyridyl-3-oxy)-pyrid-5-yl carbomyl] indoline (SB-242084) [but not the 5-HT2B antagonist 2-amino-4-(4-fluoronaphth-1-yl)-6-isopropyl-pyrimidine (RS-127445) or 5-HT2A antagonist R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)-ethyl]-4-piperidinemethanol (MDL-100907)] reversed the action of 5-HT2C receptor agonists. Furthermore, in control rats 5-HT2C receptor antagonists [SB-242084 and 5-methyl-1-(3-pyridil-carbamoyl)-1,2,3,5-tetrahydropyr-rolo[2,3-f]indole hydrochloride (SB-206553)] induced or enhanced theta oscillation in MS/DBv and hippocampal neurons and theta wave activity of the hippocampus. These findings provide evidence for a tonic regulation of the activity and theta oscillation of the septo-hippocampal system via 5-HT2C receptors in the anesthetized rat, indicating that pharmacological interactions with these receptors could modulate various physiological and pathological processes associated with limbic theta activity.

Evidence that orexin-A-evoked grooming in the rat is mediated by orexin-1 (OX1) receptors, with downstream 5-HT2C receptor involvement

Psychopharmacology (Berl) 2001 Jan 1;153(2):203-9.PMID:11205420DOI:10.1007/s002130000550.

Rationale: Orexins A and B have recently been discovered and shown to be derived from preproorexin, primarily expressed in the rat hypothalamus. Orexin-A has been ascribed a number of in vivo functions in the rat after intracerebroventricular (ICV) administration, including hyperphagia, neuroendocrine modulation and, most recently, evidence for a behavioural response characterised by an increase in grooming. Objectives: Here, we have investigated the orexin-receptor subtypes involved in the grooming response to orexin-A (3 microg, ICV) in the rat. Methods: Male rats, habituated to clear Perspex behavioural observation boxes, were pretreated with antagonists with mixed selectivity for OX1, OX2, 5-HT2B and 5-HT2C receptor subtypes prior to the administration of orexin-A and the intense grooming response elicited by this peptide assessed. Results: Pretreatment of rats with a mixed OX1/5-HT2B/2C receptor antagonist 1-(4-methylsulfanylphenyl)-3-quinolin-4-ylurea (SB-284422), revealed a significant, but incomplete, blockade of orexin-A-induced grooming. Despite the low potency of orexin-A at 5-HT2B and 5-HT2C receptors in vitro (pKi<5), studies were undertaken to determine whether downstream 5-HT2B or 5-HT2C receptors mediate in the grooming-elicited by orexin-A. Whilst the selective 5-HT2B receptor antagonist, SB-215505 (3 mg/kg, PO, 5-HT2B, pKi=8.58; OX1, pKB < 5.15) failed to effect orexin-A-induced grooming, the selective 5-HT2C receptor antagonist, SB-242084 (1 mg/kg, IP, 5-HT2C, pKi = 8.95; OX1, pKB < 5.1) potently antagonised the grooming response to this peptide. This suggested that the partial blockade of orexin-A-induced grooming obtained with SB-284422 might be attributable to its 5-HT2C and/or OX1 receptor blocking activity. However, complete blockade of orexin-A-induced grooming by the subsequently identified selective OX1 receptor antagonist 1-(2-methylbenzoxazol-6-yl)-3-[1,5]naphthyridin-4-yl urea hydrochloride, SB-334867-A (OX1, pKB = 7.4; OX2, pKB = 5.7), devoid of appreciable affinity for either 5-HT2B (pKi < 5.3) or 5-HT2C (pKi < 5.4) receptors, provides the first definitive evidence that a central behavioural effect of orexin-A (grooming) is mediated by OX1 receptors. Conclusions: This data suggests that orexin-A indirectly activates 5-HT2C receptors downstream from OX1 receptors to elicit grooming in the rat. The use of SB-334867-A in vivo will enable the role of OX,1 receptors within the rat central nervous system to be further characterised.

Effects of 5-HT2C receptor modulation and the NA reuptake inhibitor atomoxetine in tests of compulsive and impulsive behaviour

Neuropharmacology 2020 Jun 15;170:108064.PMID:32222404DOI:10.1016/j.neuropharm.2020.108064.

Drug repositioning has gained strategic value as a reaction to high attrition rates of new drugs as they pass through the clinical development process. The 5-HT2C receptor agonist lorcaserin (Belviq®), and the selective NA reuptake inhibitor atomoxetine (Strattera®) represent two drugs FDA approved for obesity and ADHD respectively. Although both drugs are of differing pharmacological class, each share a property of regulating impulsive behaviours in preclinical studies, and thus represent candidates for consideration in clinical conditions labelled as 'impulsive-compulsive disorders'. The present studies investigated both drugs, as well as the highly selective 5-HT2C agonist CP-809101 in two tests of compulsive action: schedule-induced polydipsia (SIP) and increased perseverative [PSV] (and premature [PREM]) responses emitted during an extended ITI 5-choice task. While lorcaserin (0.06-0.6 mg/kg), CP-809101 (0.1-1 mg/kg) and atomoxetine (0.1-1 mg/kg) each reduced both PREM and PSV measures in the 5-choice task, at equivalent doses only lorcaserin and CP-809101 affected excessive water intake in the SIP task, atomoxetine (0.1-2 mg/kg) was essentially ineffective. Further evidence supporting a role of the 5-HT2C receptor as an important regulator of impulsive-compulsive behaviours, the selective antagonist SB-242084 produced the opposing effects to lorcaserin, i.e promoting both impulsive and compulsive behaviours. The profile of atomoxetine may suggest differences in the nature of compulsive action measured either as non-regulatory drinking in the SIP task, and PSV responses made in a 5-choice task. These studies support the consideration of 5-HT2C receptor agonists, typified by lorcaserin, and atomoxetine as potential treatments for clinical conditions categorised as 'impulsive-compulsive disorders'. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.