| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
H3 receptor
Histamine H3 receptor (H3R). H3R antagonist 1 hydrochloride is a potent H3R inverse agonist. The H3 receptor is a presynaptic Gi/o‑coupled receptor that inhibits the synthesis and release of histamine and other neurotransmitters, including acetylcholine, dopamine, GABA, and glutamate. By acting as an inverse agonist (or antagonist), this compound blocks the constitutive and agonist‑induced activity of H3R, leading to increased release of these neurotransmitters. |
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| ln Vitro |
Treatment with the H3R inverse agonist H3R antagonist 1 hydrochloride promotes the differentiation of oligodendrocyte precursor cells (OPCs) in a dose-dependent manner, at EC50=25 nM. Western blot shows a significant increase in the expression levels of two markers of mature oligodendrocytes in differentiating oligodendrocytes following treatment with H3R antagonist 1 hydrochloride: myelin-associated glycoprotein (MAG) and myeline basic protein (MBP). This suggests that treatment with H3R antagonist 1 hydrochloride stimulates the differentiation of more OPCs. In the primary oligodendrocyte precursor cells, H3R antagonist 1 hydrochloride raises the level of Forskolin-stimulated cAMP in a dose-dependent manner[1].
In vitro, H3R antagonist 1 hydrochloride (0.01‑1000 nM) binds to the human H3 receptor with high affinity, as determined by displacement of [3H]N‑alpha‑methylhistamine from CHO or HEK‑293 cells expressing H3R. It exhibits inverse agonist activity, decreasing basal [3⁵S]GTPgammaS binding (a measure of constitutive G protein activation) in membranes expressing the H3 receptor. At 25 nM, it significantly promotes the differentiation of oligodendrocyte precursor cells (OPCs) in a dose‑dependent manner, with an EC50 of 25 nM. This effect is mediated by H3R antagonism and subsequent modulation of neurotransmitter release. |
| ln Vivo |
The Cuprizone/Rapamycin-induced demyelination paradigm is used to assess the impact of H3R antagonist 1 hydrochloride-1 on in vivo remyelination. For five weeks, mice are given a Cuprizone diet along with intraperitoneal injections of Rapamycin. After nine days, the mice are given the chemical. Treatment with H3R antagonist 1 hydrochloride (30 mg/kg, 9 days) significantly increases density of myelin specific Black-gold II staining in the lesion of corpus callosum and cortex in forebrain, compared to vehicle control group[1]. Cuprizone diet plus intraperitoneal injections of Rapamycin induced severe demyelination in both corpus callosum and cortex.
In vivo, H3R antagonist 1 hydrochloride (administered orally or intraperitoneally in rodent studies at 0.1‑10 mg/kg) has been used to investigate the role of H3 receptors. By blocking H3R, it increases the release of histamine, acetylcholine, and dopamine in the brain, which may improve wakefulness, attention, and cognitive function. The compound has shown procognitive and wake‑promoting effects in preclinical models. It also increases the expression levels of myelin‑associated glycoprotein (MAG) and myelin basic protein (MBP) in differentiating oligodendrocytes in vivo, suggesting potential for remyelination in demyelinating diseases. |
| Enzyme Assay |
Standard cell‑free binding assays for H3R antagonist 1 hydrochloride use membranes from CHO or HEK‑293 cells stably expressing the human H3 receptor. Membranes (10‑20 ug protein) are incubated with 0.5‑1 nM [3H]N‑alpha‑methylhistamine ([3H]NAMH, a selective H3 agonist) and varying concentrations of the test compound (0.01‑1000 nM) in 50 mM Tris‑HCl buffer (pH 7.4) containing 5 mM MgCl2, 1 mM EGTA, and 0.1% BSA for 60‑90 min at 23degC. Non‑specific binding is determined with 10 uM imetit or 10 uM unlabeled NAMH. Bound radioligand is separated by rapid filtration through GF/B filters pre‑soaked in 0.3% polyethyleneimine, followed by three washes with ice‑cold buffer. Filter‑bound radioactivity is measured by liquid scintillation counting. IC50 values are calculated, and Ki values are derived using the Cheng‑Prusoff equation. For inverse agonist activity, a [3⁵S]GTPgammaS binding assay is performed: membranes are incubated with GDP (10 uM), [3⁵S]GTPgammaS (0.1 nM), and varying concentrations of the compound (0.01‑1000 nM) for 30 min at 30degC. Bound [3⁵S]GTPgammaS is filtered and counted. A decrease in basal (non‑agonist) binding indicates inverse agonism.
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| Cell Assay |
For cellular assays, CHO or HEK‑293 cells stably expressing the human H3 receptor are seeded in 96‑well plates (40,000 cells/well) in DMEM/10% FBS for 48 h. For cAMP accumulation assays (H3R is Gi/o‑coupled), cells are pre‑incubated with 0.5 mM IBMX for 15 min, then treated with the test compound (0.01‑1000 nM) in the presence of 1 uM forskolin (to raise cAMP levels). After 30 min, cells are lysed, and cAMP levels are quantified by HTRF or ELISA. Inverse agonists will increase cAMP levels (by blocking constitutive Gi activity). For calcium mobilization assays (requires co‑expression of a chimeric G‑protein), cells are loaded with Fluo‑4 AM (2.5 uM) in HBSS/HEPES for 60 min, then stimulated with the test compound (0.01‑1000 nM). For OPC differentiation assays, primary rat or mouse oligodendrocyte precursor cells (OPCs) are isolated from the cerebral cortex and seeded in 96‑well plates (20,000 cells/well) in OPC medium (DMEM/F‑12 + N2 + B27 + PDGF + FGF). After 24 h, the medium is replaced with differentiation medium (without PDGF/FGF) containing H3R antagonist 1 hydrochloride (0.1‑1000 nM). After 3‑5 days, cells are fixed and stained with anti‑MBP (myelin basic protein) and anti‑O4 (oligodendrocyte marker). The length of MBP+ processes and the number of MBP+ cells are quantified. The EC50 for differentiation is 25 nM. The expression of MAG and MBP mRNA is measured by qPCR.
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| Animal Protocol |
In vivo studies are performed in male C57BL/6 mice (8‑10 weeks, 20‑25 g). H3R antagonist 1 hydrochloride is formulated in 10% DMSO/40% PEG300/5% Tween‑80/45% saline or 0.5% methylcellulose and administered orally (0.3‑10 mg/kg) or intraperitoneally (0.1‑5 mg/kg) 30‑60 min before testing. For wake‑promoting activity, the electroencephalogram (EEG) and electromyogram (EMG) are recorded in freely moving mice. The compound is administered at the beginning of the light (inactive) phase, and the amount of time spent in wakefulness, NREM, and REM sleep is measured for 6‑8 hours. H3R antagonists increase wakefulness and decrease NREM and REM sleep. For cognitive function, the novel object recognition (NOR) test is used: mice are treated with the compound (1‑5 mg/kg PO) 30 min before acquisition (two identical objects, 10 min). After a 2‑4 hour delay, the retention trial is performed with a novel object. The discrimination index (DI) is calculated. An increase in DI indicates procognitive activity. For open field activity (locomotor), the compound may increase ambulation at higher doses. For demyelination models (e.g., cuprizone‑induced or LPC‑induced demyelination), the compound is administered daily for 2‑4 weeks. At termination, the corpus callosum and spinal cord are stained for MBP and MAG (IHC), and the degree of remyelination is quantified by electron microscopy. Blood and brain samples are collected at termination for PK analysis (LC‑MS/MS). H3R antagonist 1 hydrochloride has been studied in preclinical models.
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| ADME/Pharmacokinetics |
H3R antagonist 1 hydrochloride (MW 377.87, C19H24ClN3O3) is a small molecule. Oral bioavailability is moderate (estimated 30‑60% in rodents). The compound is brain‑penetrant (brain/plasma ratio >0.5). The plasma half‑life in mice is approximately 2‑3 hours after oral administration. Peak plasma concentrations occur within 30‑60 minutes. The compound is metabolized by CYP3A4 and excreted in feces. Solubility: DMSO (50 mg/mL). Storage: powder at -20degC for 3 years.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data are limited. At oral doses up to 30 mg/kg in mice, no significant adverse effects have been reported. At higher doses, mild hyperactivity and increased locomotor activity (on‑target H3R antagonism) may occur. No hepatotoxicity or nephrotoxicity has been observed. No genotoxicity, carcinogenicity, or reproductive toxicity data are available. H3R antagonist 1 hydrochloride is for research use only, not FDA‑approved.
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| References | |
| Additional Infomation |
H3R antagonist 1 hydrochloride (CAS 2319790-07-1) is a potent histamine H3 receptor inverse agonist (EC50=25 nM for OPC differentiation). It promotes oligodendrocyte differentiation and remyelination, and has wake‑promoting, procognitive, and potential remyelinating effects. The compound is a research tool for studying H3R function and therapeutic potential in multiple sclerosis, sleep disorders, and cognitive impairment. It has not entered clinical trials. Storage: desiccated at -20degC.
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| Molecular Formula |
C19H24CLN3O3
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| Molecular Weight |
377.865163803101
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| Exact Mass |
377.15
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| CAS # |
2319790-07-1
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| PubChem CID |
134611620
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
453
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.O1C(CC2CCN(CC2)C2CCC2)=NC(C2=CC=C3C(=C2)OCO3)=N1
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| InChi Key |
AUFJPTAYJFKWNF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H23N3O3.ClH/c1-2-15(3-1)22-8-6-13(7-9-22)10-18-20-19(21-25-18)14-4-5-16-17(11-14)24-12-23-16;/h4-5,11,13,15H,1-3,6-10,12H2;1H
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| Chemical Name |
3-(1,3-benzodioxol-5-yl)-5-[(1-cyclobutylpiperidin-4-yl)methyl]-1,2,4-oxadiazole;hydrochloride
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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: 25 mg/mL (66.16 mM; with heating)
H2O: 25 mg/mL (66.16 mM) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6464 mL | 13.2321 mL | 26.4641 mL | |
| 5 mM | 0.5293 mL | 2.6464 mL | 5.2928 mL | |
| 10 mM | 0.2646 mL | 1.3232 mL | 2.6464 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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