| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Human Endogenous Metabolite
No direct pharmacological target; 3-Methylhistamine is an endogenous histamine metabolite and a biomarker. The unlabeled 3-methylhistamine is a histamine H3 receptor agonist (potency similar to histamine, Ki ~ 10-50 nM for H3R) and a weak agonist at H2 and H1 receptors. However, in research, it is primarily used as a biochemical marker rather than as a receptor ligand. It is also known to serve as a potential histamine H2-receptor antagonist and is a synthetic intermediate. |
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| ln Vitro |
3-Methylhistamine (the unlabeled compound) is a histamine metabolite that serves as a stable biomarker for histamine release and mast cell activation in vivo. It is one of the primary metabolites of histamine, formed by the enzyme histamine N-methyltransferase (HNMT), and is excreted in urine. Plasma and urinary 3-methylhistamine levels correlate well with histamine release, making it a more reliable indicator of histamine turnover than histamine itself, which is rapidly metabolized. In vitro, 3-methylhistamine shows upregulation in vaccinated mice, indicating an association with immune response. 3-Methylhistamine has also been reported to have histamine H3 receptor agonist activity and weak H2-receptor antagonist properties.
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| ln Vivo |
As a histamine metabolite, 3-methylhistamine is used to measure histamine release in vivo. Elevated levels of 3-methylhistamine in plasma or urine are observed in allergic reactions, mastocytosis, anaphylaxis, and other conditions involving mast cell and basophil degranulation. In animal models of inflammation, histamine N-methyltransferase (HNMT) activity and 3-methylhistamine levels change in response to histamine-releasing stimuli. In vaccinated mice, 3-methylhistamine levels are upregulated, indicating its involvement in immune responses. The compound is used as a stable non-invasive biomarker to monitor mast cell activation and histamine turnover.
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| Enzyme Assay |
No specific enzyme/receptor binding protocol. 3-Methylhistamine is an endogenous histamine metabolite, not a direct enzyme/substrate for in vitro binding assays unless used as a standard for competition studies. For histamine N-methyltransferase (HNMT) activity assay: (1) Incubate recombinant human HNMT (1-10 ug) with histamine (10-1000 uM) and S-adenosyl-L-methionine (SAM, 100 uM) in 50 mM phosphate buffer (pH 7.9) at 37degC for 30-60 min. (2) Terminate the reaction by adding 10% perchloric acid, centrifuge. (3) Separate and quantify 3-methylhistamine by HPLC with fluorescence detection or LC-MS/MS. (4) For receptor binding: Perform radioligand binding with [3H]-histamine or [3H]-Nalpha-methylhistamine to histamine receptor subtypes (H1, H2, H3, H4) in membrane preparations. Use 3-methylhistamine (0.1 nM-100 uM) as a competitor to determine Ki values.
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| Cell Assay |
(1) For 3-methylhistamine as a biomarker: seed mast cells (e.g., RBL-2H3 or primary peritoneal mast cells) in 24-well plates overnight. (2) Stimulate cells to degranulate using compound 48/80 (10 ug/mL), ionophore A23187 (1 uM), or IgE/antigen cross-linking for 30-60 min. (3) Collect cell supernatant, perform protein precipitation with acetonitrile (1:1), centrifuge. (4) Quantify 3-methylhistamine in supernatant by LC-MS/MS or competitive ELISA. (5) For histamine metabolism: treat cells with histamine (0.1-100 uM) for 0-24 h, add cell lysates to reaction buffer with SAM, measure 3-methylhistamine formation as a readout of HNMT activity. (6) For immune response studies: treat immune cells (e.g., splenocytes or bone marrow-derived mast cells) with vaccines or immune stimuli, measure 3-methylhistamine levels by LC-MS as a biomarker of histamine release.
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| Animal Protocol |
(1) Use 6-8 week old male C57BL/6 mice (20-25 g) or Sprague-Dawley rats (200-250 g). (2) Induce histamine release by administering compound 48/80 (0.2-1 mg/kg, IP) or by active systemic anaphylaxis (OVA sensitization and challenge). (3) Collect blood at 15, 30, 60, 120 min post-stimulation by cardiac puncture into EDTA-coated tubes. (4) For urine studies: house animals in metabolic cages and collect 24-h urine samples. (5) Process plasma or urine samples: add 3 volumes of acetonitrile containing internal standard (3-methylhistamine-d3 or 3-methylhistamine-d4), vortex, centrifuge at 14,000 rpm for 10 min. (6) Analyze by LC-MS/MS: separate on a HILIC or C18 column (2.1 × 100 mm, 3.5 um) with mobile phase of 0.1% formic acid in water/acetonitrile (gradient elution). (7) Quantify 3-methylhistamine concentration using isotope dilution mass spectrometry. (8) Compare levels between control and treated groups to assess histamine release.
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| ADME/Pharmacokinetics |
Standard formulation for 3-methylhistamine dihydrochloride as an analytical standard: prepare stock solution in water or 0.1% formic acid in water at 1 mg/mL. For LC-MS analysis, dilute stock in 0.1% formic acid/water to prepare calibration standards (1-1000 ng/mL). For in vitro treatment: dissolve in water or PBS (pH 7.4) at 1-100 mM, filter sterilize. The dihydrochloride salt is highly soluble in water (≥ 50 mg/mL). Storage: store powder at -20degC for 3 years, protected from light; in solvent at -80degC for 6 months, -20degC for 1 month. Avoid repeated freeze-thaw cycles. The compound is chemically stable under these conditions.
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| Toxicity/Toxicokinetics |
3-Methylhistamine is an endogenous histamine metabolite and is considered non-toxic at physiological concentrations (normal plasma levels: 0.1-1 ng/mL; urine excretion: 10-100 ug/24 h). The dihydrochloride salt has low acute toxicity. In vitro: CCK-8 assay on HEK293 cells with 3-methylhistamine dihydrochloride (1-1000 uM) shows IC50 > 500 uM for 48 h. In vivo toxicity: oral LD50 in rodents > 2000 mg/kg. IP administration (100 mg/kg) in mice shows no overt toxicity or weight loss. The compound is intended for research use only, not for human therapeutic use.
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| References |
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| Additional Infomation |
3-Methylhistamine dihydrochloride is a stable histamine metabolite used as a biomarker for histamine release in research studies of allergic diseases, mast cell activation disorders, anaphylaxis, and immune responses. It is formed by histamine N-methyltransferase (HNMT)-mediated methylation of histamine at the Nτ position. Plasma and urinary 3-methylhistamine levels are more reliable indicators of histamine release than histamine itself due to the short half-life of histamine (1-2 min). This compound is not a drug and is not FDA-approved; it is strictly for research use as an analytical standard, biomarker, and for histamine metabolism studies. The dihydrochloride salt form enhances solubility and stability for laboratory applications.
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| Molecular Formula |
C6H13CL2N3
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|---|---|
| Molecular Weight |
198.09
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| Exact Mass |
197.049
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| CAS # |
36475-47-5
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| PubChem CID |
16219689
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| Appearance |
Off-white to light yellow solid powder
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| Boiling Point |
353.3ºC at 760 mmHg
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| Melting Point |
268-270ºC
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| Flash Point |
167.5ºC
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| LogP |
2.225
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
11
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| Complexity |
84.4
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1C=NC=C1CCN.Cl.Cl
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| InChi Key |
KWEIZIDNCJBKIY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C6H11N3.2ClH/c1-9-5-8-4-6(9)2-3-7;;/h4-5H,2-3,7H2,1H3;2*1H
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| Chemical Name |
2-(3-methylimidazol-4-yl)ethanamine;dihydrochloride
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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 :~12.5 mg/mL (~63.10 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (6.31 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 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: ≥ 1.25 mg/mL (6.31 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 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: ≥ 1.25 mg/mL (6.31 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 | 5.0482 mL | 25.2411 mL | 50.4821 mL | |
| 5 mM | 1.0096 mL | 5.0482 mL | 10.0964 mL | |
| 10 mM | 0.5048 mL | 2.5241 mL | 5.0482 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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