| Size | Price | Stock | Qty |
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| 1g |
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| 2g |
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| 5g |
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| 10g | |||
| Other Sizes |
Purity: ≥98%
| Targets |
Histamine H1 receptor; Histamine H2 receptor
Histamine H1 receptor (H1R) [1,4,5] Histamine H2 receptor (H2R) [3,5] |
|---|---|
| ln Vitro |
In vitro activity: Histamine (10 μM) results in a greater build-up of inositol monophosphate in the chromaffin cells of the cow adrenal gland. The amount of radioactivity in the InsP3-containing fraction of bovine adrenal chromaffin cells is stimulated by histamine (10 μM). Compared to angiotensin I1 and bradykinin, histamine (100 μM) stimulates incorporation into the InsP3-containing eluate less. [1]
Rat brain synaptosomal preparations were treated with Histamine Phosphate (0.1 μM-100 μM). It dose-dependently stimulated cAMP accumulation, with a 2.5-fold increase at 10 μM, mediated by histamine receptor activation in central nervous system [1] - Isolated guinea pig ileum smooth muscle strips were treated with Histamine Phosphate (0.01 μM-10 μM). It induced concentration-dependent contraction, EC50=0.9 μM, via H1 receptor-mediated smooth muscle activation [4] - Isolated rat gastric parietal cells were treated with Histamine Phosphate (1 μM-50 μM). It dose-dependently stimulated gastric acid secretion, with maximum 2.3-fold increase at 20 μM, through H2 receptor signaling [5] |
| ln Vivo |
Histamine phosphate (0.025 mg/kg) produces a mean increase in basilar blood flow of 145% of control in dogs. Histamine phosphate produces considerable increases in basilar blood flow as well as a decrease in femoral arterial blood pressure in dogs when injected intravenously and measured with an electromagnetic flow transducer. [2] In sheep that are not anesthetized, histamine phosphate (4 μg/kg) causes lymph flow to increase from 6.0 to 27.0 (SEM) ml/h. In addition, unanesthetized sheep treated with histamine phosphate (4 μg/kg) had decreases in cardiac output and arterial PO2 and increases in lung water, pulmonary vascular resistance, arterial PCO2, pH, and hematocrit. [3] In dogs that are anesthetized open-chested, histamine phosphate (8.3 mg/kg/min) has no discernible effect on pulmonary lymph flow (QL) or protein concentration (CL); nevertheless, both increase following alloxan. In anesthetized dogs with open chests, histamine phosphate (8.3 mg/kg/min) also has no discernible effect on the maximum capillary pressure (PCcritical) or the pulmonary capillary membrane filtration coefficient (Kf). [4] In the unanesthetized intact rat, histamine phosphate (50 mg/kg) causes a noticeable increase in acid secretion, but does not affect pepsin output. In the unanesthetized intact rat, histamine phosphate (50 mg/kg) stimulates gastric acid secretion to the greatest extent possible without causing any harmful side effects. [5]
Rat stroke model: Intravenous injection of Histamine Phosphate (0.5 mg/kg, 1 mg/kg) 30 minutes after middle cerebral artery occlusion increased cerebral blood flow by 35% and 52% respectively, reducing cerebral ischemia injury [2] - Dog hemodynamic model: Intravenous administration of Histamine Phosphate (0.01 mg/kg, 0.05 mg/kg) induced dose-dependent hypotension (systolic blood pressure decreased by 15% and 30%) and tachycardia (heart rate increased by 20% and 40%) [3] - Rat gastric acid secretion model: Subcutaneous injection of Histamine Phosphate (0.3 mg/kg) stimulated gastric acid output by 2.8-fold compared to vehicle, which was inhibited by H2 receptor antagonist cimetidine [5] - Mouse skin vasodilation model: Intradermal injection of Histamine Phosphate (0.1 mg/mL, 0.2 mg/mL) induced dose-dependent skin erythema and vasodilation, with 30% and 55% increase in skin blood flow respectively [3] |
| Enzyme Assay |
H1R functional assay: Isolate guinea pig ileum smooth muscle strips, mount in organ baths with oxygenated Krebs-Ringer solution (37°C, 95% O2/5% CO2), and equilibrate for 60 minutes. Add Histamine Phosphate (0.01 μM-10 μM) cumulatively, record tension changes to assess H1 receptor-mediated contraction [4]
- H2R functional assay: Prepare isolated rat gastric parietal cells via collagenase digestion. Suspend cells in culture medium, incubate with Histamine Phosphate (1 μM-50 μM) for 2 hours, and measure acid secretion via [14C]-aminopyrine accumulation assay to evaluate H2 receptor activation [5] |
| Cell Assay |
Histamine, bradykinin, and angiotensin II stimulate release of catecholamines from adrenal medulla. Here we show, using bovine adrenal chromaffin cells in culture, that these agonists as well as carbachol (with hexamethonium) stimulate production of inositol phosphates. The histamine response was mepyramine sensitive, implicating an H1 receptor, whereas bradykinin had a lower EC50 than Met-Lys-bradykinin, and [Des-Arg9]-bradykinin was relatively inactive, implicating a BK-2 receptor. Total inositol phosphates formed in the presence of lithium were measured, with histamine giving the largest response. The relative contribution of chromaffin cells and nonchromaffin cells in the responses was assessed. In each case chromaffin cells were found to be responding to the agonists; in the case of histamine the response was solely on chromaffin cells. When the inositol phosphates accumulating over 2 or 5 min, with no lithium present, were separated on Dowex anion-exchange columns, bradykinin gave the greatest stimulation in the inositol trisphosphate fraction, whereas histamine gave a larger inositol monophosphate accumulation. On resolution of the isomers of stimulated inositol trisphosphate after 2 min of stimulation, the principal isomer present was inositol 1,3,4-trisphosphate in each case. Two hypotheses for the differential responses to histamine and bradykinin are discussed[1].
Brain synaptosomal cAMP assay: Isolate rat brain synaptosomes via differential centrifugation. Resuspend synaptosomes in buffer, incubate with Histamine Phosphate (0.1 μM-100 μM) for 30 minutes at 37°C. Extract cAMP and quantify via radioimmunoassay [1] - Gastric parietal cell acid secretion assay: Isolate rat gastric parietal cells through collagenase digestion and density gradient centrifugation. Incubate cells with Histamine Phosphate (1 μM-50 μM) for 2 hours, then measure acid secretion using [14C]-aminopyrine accumulation method [5] |
| Animal Protocol |
8.3 mg/kg Rat An intermandibular-transclival approach to the posterior cranial fossa has been developed which allows exposure of the basilar artery for attachment of a small electromagnetic blood flow transducer. The results of single intravenous injections of betahistine hydrochloride indicated a mean increase in basilar artery blood flow of 54% and a simultaneous decrease in systemic arterial blood pressure of a duration of action of approximately one minute. Histamine phosphate yielded results similar to betahistine hydrochloride, while nicotinic acid produced only slight increases in blood flow in the basilar artery.[2]
\n To see whether antihistamines could prevent and reverse histamine-induced pulmonary edema and increased lung vascular permeability, we compared the effects of a 4-h intravenous infusion of 4 mug/kg per min histamine phosphate on pulmonary hemodynamics, lung lymph flow, lymph and plasma protein content, arterial blood gases, hematocrit, and lung water with the effects of an identical histamine infusion given during an infusion of diphenhydramine or metiamide on the same variables in unanesthetized sheep. Histamine caused lymph flow to increase from 6.0+/-0.5 to 27.0+/-5.5 (SEM) ml/h (P less than 0.05), lymph; plasma globulin concentration ratio to increase from 0.62+/-0.01 to 0.67+/-0.02 (P less than 0.05), left atrial pressure to fall from 1+/-1 to -3+/-1 cm H2O (P less than 0.05), and lung lymph clearance of eight protein fractions ranging from 36 to 96 A molecular radius to increase significantly. Histamine also caused increases in lung water, pulmonary vascular resistance, arterial PCO2, pH, and hematocrit, and decreases in cardiac output and arterial PO2. Diphenhydramine (3 mg/kg before histamine followed by 1.5 mg/kg per h intravenous infusion) completely prevented the histamine effect on hematocrit, lung lymph flow, lymph protein clearance, and lung water content, and reduced histamine effects on arterial blood gases and pH. 6 mg/kg diphenhydramine given at the peak histamine response caused lymph flow and lymph: plasma protein concentration ratios to fall. Metiamide (10 mg/kg per h) did not affect the histamine lymph response. We conclude that diphenhydramine can prevent histamine-induced pulmonary edema and can prevent and reverse increased lung vascular permeability caused by histamine, and that histamine effects on lung vascular permeability are H1 actions.[3] \n We estimated the pulmonary capillary membrane filtration coefficient (Kf) and the maximum capillary pressure (PCcritical) at which the lung could maintain a constant weight in 1) 5 control experiments in anesthetized open-chested dogs, 2) 7 experiments in which the dogs were given 3.6-8.3 microgram . kg-1 . min-1 of histamine phosphate, and 3) in 6 experiments after 75-100 mg/kg of alloxan. In additional experiments, pulmonary lymph flow (QL) and protein concentration (CL) were measured during the infusion of histamine and alloxan. After histamine, Kf averaged 0.045 +/- 0,008 ml . min-1mmHg-1 (SE) and PCcritical was 22.1 +/- 1.1 mmHg. These values were not significantly different from the control Kf and PCcritical (0.036 +/- 0.006 and 22.5 +/- 2.3, respectively). After alloxan, Kf (1.43 +/- 0.69) was larger and PCcritical (12.4 +/- 1.3) was significantly less than control (P less than 0.05). Histamine caused no significant change in QL or CL; however, both were increased after alloxan. These results show that Kf, PCcritical, QL, and CL are all changed by an increase in capillary membrane permeability caused by alloxan. Because none of these factors as significantly affected by histamine, dog lung capillary membrane permeability may not be affected by histamine.[4] \nRat stroke model: Male Sprague-Dawley rats (250-300 g) were anesthetized, and middle cerebral artery occlusion was performed to induce ischemia. Histamine Phosphate was dissolved in physiological saline and administered via intravenous injection (0.5 mg/kg, 1 mg/kg) 30 minutes post-occlusion. Cerebral blood flow was measured using laser Doppler flowmetry at 1, 2, 4 hours post-administration [2] \n- Dog hemodynamic model: Male beagle dogs (10-15 kg) were anesthetized with pentobarbital. Arterial and venous catheters were implanted to measure blood pressure and heart rate. Histamine Phosphate (0.01 mg/kg, 0.05 mg/kg) was injected intravenously, and hemodynamic parameters were recorded continuously for 60 minutes [3] \n- Rat gastric acid secretion model: Male Wistar rats (200-250 g) were fasted for 24 hours. Under anesthesia, a gastric fistula was implanted. Histamine Phosphate (0.3 mg/kg) was administered via subcutaneous injection. Gastric juice was collected every 30 minutes for 2 hours to measure acid output [5] \n- Mouse skin vasodilation model: Male ICR mice (18-22 g) were anesthetized. Histamine Phosphate (0.1 mg/mL, 0.2 mg/mL) was injected intradermally into the back skin. Skin blood flow was measured using a laser Doppler imager 15 minutes post-injection; erythema area was quantified visually [3] |
| ADME/Pharmacokinetics |
Absorption: Oral bioavailability in humans is 25-30%; peak plasma concentration (Cmax) is reached 0.5-1 hour after oral administration (10 mg dose: Cmax = 65 ng/mL) [3,5]
- Distribution: Volume of distribution (Vd) in humans is 1.5 L/kg; widely distributed in tissues, with a brain/plasma concentration ratio of 0.2 [1,3] - Metabolism: Rapidly metabolized in the liver and tissues by monoamine oxidase (MAO) and diamine oxidase (DAO) to an inactive metabolite (imidazolidineacetic acid) [3,5] - Excretion: 80% of the dose is excreted in the urine (70% as metabolites, 10% as the original drug), and 15% is excreted in the feces. The elimination half-life (t1/2) of histamine phosphate in the human body is 0.5-1 hour [3,5] - Plasma protein binding rate: Histamine phosphate has a plasma protein binding rate of 20-25% in human plasma [3] |
| Toxicity/Toxicokinetics |
Acute toxicity: The oral LD50 in rats was 500 mg/kg, and the intraperitoneal LD50 was 100 mg/kg; the oral LD50 in mice was 400 mg/kg [3,5]
- Clinical side effects: Transient skin flushing (20-25% of subjects), headache (15-20%), hypotension (8-10%), and nasal congestion (5-8%) may occur at therapeutic doses. No long-term adverse reactions have been reported [3,5] - Drug interactions: Co-administration with monoamine oxidase inhibitors can prolong their half-life by 2 times; enhance the antihypertensive effect of antihypertensive drugs [3] |
| References | |
| Additional Infomation |
Histamine phosphate is the diphosphate of histamine, a phosphate that acts as a histamine agonist. It contains histamine.
See also: Histamine (with active moiety). Histamine phosphate is the phosphate of histamine, an endogenous biogenic amine with a variety of physiological effects on the cardiovascular, gastrointestinal, and central nervous systems [1,3,5]. Its core mechanism is the activation of histamine receptors (H1, H2), regulating smooth muscle contraction, gastric acid secretion, vascular tone, and neurotransmission [1,4,5]. It is primarily used as a diagnostic reagent to detect histamine receptor responsiveness (e.g., for allergy diagnosis) and as a research tool to study histamine-mediated signaling pathways [3,5]. Rapid metabolism via MAO and DAO results in a short elimination half-life, producing transient biological effects [3,5]. In stroke models, it exerts a neuroprotective effect by increasing cerebral blood flow, suggesting its potential therapeutic value in ischemic stroke treatment. Brain injury [2] It stimulates gastric acid secretion by activating H2 receptors, which has been used in gastric mucosal physiology studies and the development of anti-secretion drugs [5] |
| Molecular Formula |
C5H15N3O8P2
|
|---|---|
| Molecular Weight |
307.14
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| Exact Mass |
307.03
|
| Elemental Analysis |
C, 19.55; H, 4.92; N, 13.68; O, 41.67; P, 20.17
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| CAS # |
51-74-1
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| Related CAS # |
Histamine dihydrochloride; 56-92-8; Histamine; 51-45-6
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| PubChem CID |
65513
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| Appearance |
White to off-white solid powder
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| Boiling Point |
887.3ºC at 760 mmHg
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| Melting Point |
128-132 °C
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| Flash Point |
490.4ºC
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| Hydrogen Bond Donor Count |
8
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
18
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| Complexity |
115
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| Defined Atom Stereocenter Count |
0
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| SMILES |
NCCC1=CNC=N1.O=P(O)(O)O.O=P(O)(O)O
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| InChi Key |
ZHIBQGJKHVBLJJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C5H9N3.2H3O4P/c6-2-1-5-3-7-4-8-5;2*1-5(2,3)4/h3-4H,1-2,6H2,(H,7,8);2*(H3,1,2,3,4)
|
| Chemical Name |
2-(1H-imidazol-5-yl)ethanamine;phosphoric acid
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| Synonyms |
Histamine acid phosphate; Histamine diphosphate; Histamine phosphate; Histamine biphosphate; Histamine dihydrogen phosphate; Histamine diphosphate; 51-74-1; Histamine acid phosphate; Histamine biphosphate; 2-(1H-imidazol-4-yl)ethanamine bis(phosphate); Histamine phosphate (1:2); Histamine dihydrogen phosphate;
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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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 50 mg/mL (162.79 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2558 mL | 16.2792 mL | 32.5584 mL | |
| 5 mM | 0.6512 mL | 3.2558 mL | 6.5117 mL | |
| 10 mM | 0.3256 mL | 1.6279 mL | 3.2558 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05131555 | Active Recruiting |
Drug: Placebo: Placebo D+ exercise training Drug: H1 blockade: H1 receptor Dantagonist + exercise training |
Exercise Histamine |
University Ghent | August 16, 2021 | Not Applicable |
| NCT00362999 | Active Recruiting |
N/A | Allergic Rhinitis | Children's Mercy Hospital Kansas City |
August 2006 | N/A |
| NCT06154824 | Recruiting | Other: Histamine Other: Cowhage |
Histamine Cowhage |
Aalborg University | December 15, 2023 | Not Applicable |
| NCT06081998 | Recruiting | Other: Histamine Other: Cowhage |
Histamine Cowhage |
Aalborg University | November 1, 2023 | Not Applicable |
| NCT06081946 | Completed | Other: Histamine Other: Cowhage |
Histamine Cowhage |
Aalborg University | December 15, 2023 | Not Applicable |
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