| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 250mg |
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Purity: ≥98%
SB 399885 hydrochloride is a novel, potent, brain penetrant, and orally bioactive 5-HT6 receptor antagonist. It exhibits selectivity for SR-6 over other serotonin receptors by more than 200 times (pKi values for human recombinant, native rat, and native human SR-6 receptors, respectively, are 9.11, 8.81, and 9.02). Blockade of postsynaptic 5-HT₆ receptors with systemic administration of SB-399885 and RO-4368554 increases W and reduces SWS and REMS during the light phase of the sleep-wake cycle. Moreover, SB-399885 suppresses REMS during the dark phase. Furthermore, it was established that giving the rat the 5-HT(2A) receptor antagonist EMD 281014 increases SWS in both light-dark cycle phases.
| Targets |
5-HT6 Receptor
SB-399885 is a selective antagonist of the serotonin 5-HT6 receptor. [1] |
|---|---|
| ln Vivo |
SB-399885 hydrochloride 10 mg/kg, when compared to the control vehicle, significantly increases wakefulness (W) (F(3,15)=3.32, P<0.05), while REM sleep, slow wave sleep, and the number of REM periods decrease (F(3,15)=4.0, P<0.01; F(3,15)=3.14, P<0.05, and F(3,15)=2.62, P<0.05, respectively). According to an analysis of sleep variables in 2-hour blocks, during the first 2-hour period, SB-399885 hydrochloride 10 mg/kg increases W (F(3,15)=5.48, P<0.01) and decreases SWS (F(3,15)=5.42, P<0.01) and REMS (F(3,15)= 4.05, P<0.01). Light sleep is enhanced by SB-399885 hydrochloride at doses of 5 and 10 mg/kg during the first (F(3,15)=3.46, P<0.01 and F(3,15)= 3.65, P<0.01, respectively) and second (F(3,15)=3.23, P<0.05 and F(3,15)=3.08, P<0.05) 2-hour recording periods. SB-399885 hydrochloride 10 mg/kg significantly increases REMS latency (F(3,15)=3.60, P<0.01) and reduces the number of REM periods during the first 2-h of recording (F(3,15)=3.88, P<0.01)[1].
Systemic administration (i.p.) of SB-399885 (10 mg/kg) 2 hours after the beginning of the light phase in rats significantly increased wakefulness (W) and reduced slow wave sleep (SWS), REM sleep (REMS), and the number of REM periods during 6-hour recording sessions. Light sleep was increased across the entire dose range (2.5, 5, 10 mg/kg). The increase in W and reduction in SWS and REMS occurred predominantly during the first 2-hour period post-injection, while light sleep was augmented during the first and second 2-hour periods. [1] Administration of SB-399885 (10 mg/kg) 2 hours after the beginning of the dark phase induced a significant reduction of REMS during the first 2-hour recording period, with no significant changes in other sleep variables over the 6-hour session. [1] The study suggests that the effects of SB-399885 on the sleep-wake cycle are receptor-dependent, as similar waking-promoting and sleep-reducing effects were observed with another 5-HT6 receptor antagonist, RO-4368554, during the light phase. [1] |
| Animal Protocol |
At the time of surgery, twelve male Wistar rats weighing between 350 and 400 g are utilized. For four weeks, beginning two hours after the start of the dark period, animals acclimated to a 12-hour light/12-hour dark cycle are given intraperitoneally SB-399885 hydrochloride 2.5, 5 and 10 mg/kg or a vehicle (1% aqueous solution of Tween 80) (n = 6). All twelve treatments are given to each animal. 15 minutes later, recordings start, and they last for 6 hours. Give the control solution and hydrochloride of SB-399885 no less than three days apart[1].
Adult male Wistar rats (350-400 g) were surgically implanted under sterile conditions with electrodes for chronic polysomnographic recordings of electroencephalogram (EEG) and electromyogram (EMG). Animals were housed individually in a temperature-controlled room on a 12-hour light/12-hour dark cycle. For experiments during the light phase, SB-399885 (2.5, 5, 10 mg/kg) or vehicle (1% aqueous Tween 80) was administered intraperitoneally (i.p.) 2 hours after lights-on. For experiments during the dark phase, drugs were administered i.p. 2 hours after lights-off to animals adapted to a reversed light-dark cycle for 4 weeks. Polysomnographic recordings began 15 minutes post-injection and continued for 6 hours. Sleep stages (wakefulness, light sleep, SWS, REMS) were scored visually in 10-second epochs. A repeated measures ANOVA with Dunnett's post-hoc test was used for statistical analysis. Each animal received all treatments in a balanced order, with at least a 3-day washout period between treatments. [1] |
| References | |
| Additional Infomation |
5-HT6 receptor is a G protein-coupled receptor that is positively coupled to adenylate cyclase and located postsynaptic in brain regions involved in sleep-wake regulation, such as the cerebral cortex, hippocampus, striatum, and hypothalamus. [1] 5-HT6 receptor antagonists, including SB-399885, have been thought to enhance cognitive function. Other neurochemical studies have suggested that sleep-wake changes caused by 5-HT6 receptor blockade may be associated with elevated levels of acetylcholine, glutamate, norepinephrine, and dopamine in key brain regions, such as the frontal cortex and hippocampus, although this study did not directly confirm this specific mechanism. [1] This study concluded that SB-399885 blocks central 5-HT6 receptors, promoting wakefulness and inhibiting sleep, which is the opposite of the sleep-promoting (enhancing slow-wave sleep) effect of 5-HT2A receptor antagonists. [1]
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| Molecular Formula |
C18H22CL3N3O4S
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|---|---|
| Molecular Weight |
482.8090
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| Exact Mass |
481.039
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| Elemental Analysis |
C, 44.78; H, 4.59; Cl, 22.03; N, 8.70; O, 13.26; S, 6.64
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| CAS # |
402713-81-9
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| Related CAS # |
SB399885; 402713-80-8
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| PubChem CID |
10277652
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
29
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| Complexity |
600
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1=C([H])C(=C([H])C(=C1OC([H])([H])[H])N([H])S(C1C([H])=C([H])C(=C(C=1[H])N1C([H])([H])C([H])([H])N([H])C([H])([H])C1([H])[H])OC([H])([H])[H])(=O)=O)Cl.Cl[H]
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| InChi Key |
RNKCEBCFUSXSQE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H21Cl2N3O4S.ClH/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;1H
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| Chemical Name |
N-(3,5-dichloro-2-methoxyphenyl)-4-methoxy-3-piperazin-1-ylbenzenesulfonamide;hydrochloride
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| Synonyms |
SB399885 HCl; SB399885; SB399885 hydrochloride; SB 399885; SB-399885
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~100 mg/mL (~207.1 mM)
H2O: ~6.7 mg/mL (~13.8 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.18 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (5.18 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.18 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0712 mL | 10.3560 mL | 20.7121 mL | |
| 5 mM | 0.4142 mL | 2.0712 mL | 4.1424 mL | |
| 10 mM | 0.2071 mL | 1.0356 mL | 2.0712 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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