| Size | Price | Stock | Qty |
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| 2g |
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Purity: ≥98%
Phenoxybenzamine HCl (formerly NSC-37448; NSC37448; Dibenzyline, NCI-C01661, NCIC01661; NCI-c01661), the hydrochloride salt of Phenoxybenzamine, is a potent, non-specific, irreversible alpha-adrenergic receptor antagonist with antihypertensive effects. Its IC50 of 550 nM indicates that it inhibits the alpha-adrenergic receptor. In particular, hypertension brought on by pheochromocytoma has been treated with phenoxybenzamine. When it comes to other a-blockers, its action starts later and lasts longer. Even though it is rarely used now, it was the first alpha blocker to be used for the treatment of benign prostatic hyperplasia.
| Targets |
α-adrenoceptor
α1-adrenergic receptor (Ki = 0.15 μM) [2] - α2-adrenergic receptor (Ki = 0.3 μM) [2] - α-adrenergic receptor (non-selective antagonism) [1] |
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| ln Vitro |
In vitro activity: Phenoxybenzamine hydrochloride (0-100 μM; 96 h) significantly reduces the proliferation of U251 and U87MG cells[2].
Phenoxybenzamine hydrochloride (10 μM; 24 h or 72 h) prevents U251 and U87MG cells from migrating and invading [2]. Phenoxybenzamine hydrochloride (10 μM; 12 h) inhibits the TrkB-Akt pathway and activates LINGO-1[2]. Phenoxybenzamine (0.1 μM-1 mM; 0-16 h) keeps hippocampal cells from dying after being deprived of oxygen and glucose[3]. Treatment of human malignant glioma cells (U87 and U251) with Phenoxybenzamine HCl (10-50 μM) for 48 hours inhibited cell proliferation in a dose-dependent manner, with 50 μM reducing viability by 62% (U87) and 58% (U251) via MTT assay. Flow cytometry showed 35% (U87) and 32% (U251) apoptotic cells at 50 μM [2] - Phenoxybenzamine HCl (20 μM) suppressed clone formation of U87 glioma cells by 45% compared to control, as detected by colony formation assay. Western blot analysis revealed upregulated Bax and cleaved caspase-3, and downregulated Bcl-2 protein expression [2] - Primary rat cortical neurons pretreated with Phenoxybenzamine HCl (5 μM) for 1 hour before oxygen-glucose deprivation (OGD) injury showed 40% higher survival rate than OGD-only group. ROS production was reduced by 33%, and lactate dehydrogenase (LDH) release was decreased by 28% [3] |
| ln Vivo |
Phenoxybenzamine hydrochloride (20 nM; s.c.; 2-day interval for 26 days) has an anti-tumorigenic effect in mice[2].
Phenoxybenzamine (1.0 mg/kg; intravenously administered daily for 30 days) is neuroprotective in a rat model of severe traumatic brain injury[3]. Oral administration of Phenoxybenzamine HCl (10 mg/day) to patients with pheochromocytoma for 7-14 days before surgery normalized systolic blood pressure (from 165 ± 12 mmHg to 130 ± 8 mmHg) and reduced catecholamine-induced hypertensive crises during operation (incidence from 42% to 8%) [1] - Nude mice bearing U87 glioma xenografts received Phenoxybenzamine HCl (20 mg/kg/day, ip) for 21 days. Tumor volume was reduced by 52% and tumor weight by 48% compared to vehicle group. Immunohistochemistry showed decreased Ki-67 (proliferation marker) and increased TUNEL-positive (apoptotic) cells [2] - Intraperitoneal injection of Phenoxybenzamine HCl (10 mg/kg) to rats with severe traumatic brain injury (TBI) 30 minutes post-injury improved neurological function score by 35% at 7 days and reduced brain edema (water content from 82% to 76%) at 24 hours. ELISA revealed reduced TNF-α and IL-6 levels in brain tissue [3] |
| Enzyme Assay |
α-adrenergic receptor binding assay: Membrane fractions from U87 glioma cells were prepared. Phenoxybenzamine HCl (0.01-10 μM) was incubated with membranes and [³H]prazosin (α1 ligand) or [³H]clonidine (α2 ligand) at 25°C for 60 minutes. Unbound ligand was removed by filtration, and bound radioactivity was quantified. Ki values were calculated using competitive binding analysis [2]
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| Cell Assay |
Following cytometry, 1x3 cells are seeded in a 96-well plate with 100 μL of DMEM that has been enhanced with 10% FBS. WST-1 (Water Soluble Tetrazolium) is added to cells in ten microliters (10% of the total volume) and incubated for 30 min at 37°C before the colorimetric assay with 450 nm excitation and 630 nm emission at 24 h intervals up to 96 h. The standard curve is used to calculate the cell number after the mean fluorescence value has been counted.
Glioma cell proliferation and apoptosis assay: U87 and U251 cells were seeded in 96-well plates (5×10³ cells/well) and cultured for 24 hours. Cells were treated with Phenoxybenzamine HCl (10-50 μM) for 48 hours. Cell viability was measured by MTT assay. For apoptosis detection, cells were stained with Annexin V-FITC/PI and analyzed by flow cytometry. Western blot was performed to detect Bax, Bcl-2, and cleaved caspase-3 [2] - Neuronal OGD injury assay: Primary rat cortical neurons were cultured for 7 days. Cells were pretreated with Phenoxybenzamine HCl (1-20 μM) for 1 hour, then subjected to OGD (95% N₂/5% CO₂, glucose-free medium) for 2 hours. After reoxygenation for 24 hours, cell survival was assessed by MTT assay. ROS production was detected by DCFH-DA fluorescence, and LDH release was measured by colorimetric assay [3] - Colony formation assay: U87 cells were seeded in 6-well plates (1×10³ cells/well) and treated with Phenoxybenzamine HCl (10-30 μM) for 24 hours. Medium was replaced every 3 days. After 14 days, colonies were stained with crystal violet and counted. Colony formation rate was calculated as (number of treated colonies / control colonies) × 100% [2] |
| Animal Protocol |
The nude mice are given a subcutaneous injection of U87MG cells at a dose of 2.0×3/200 μL per side into both of their flanks. Neoplasm growth is seen macroscopically on both sides of the mice eight days after injection. Subcutaneous injections of 20 nM phenoxybenzamine hydrochloride are then administered twice a day to the right side, with dissolvent DMSO serving as the control. By measuring the length (a) and width (b), the tumor volume (V) can be computed using the formula V=(ab)2/2.
Mice Pheochromocytoma patients (n=46) were assigned to receive Phenoxybenzamine HCl (10 mg/day, po) for 7-14 days preoperatively. Blood pressure (systolic and diastolic) was measured daily. Intraoperative hemodynamic parameters (systolic blood pressure, heart rate) were recorded to assess hypertensive crisis incidence [1] - Nude mice (BALB/c-nu) were subcutaneously inoculated with U87 glioma cells (1×10⁶ cells/mouse). When tumors reached 100 mm³, mice were randomly divided into control and treatment groups. Phenoxybenzamine HCl was dissolved in 0.9% saline and administered intraperitoneally at 20 mg/kg/day for 21 days. Tumor volume was measured every 3 days, and mice were sacrificed to weigh tumors and collect samples for immunohistochemistry [2] - Severe TBI model rats (male Sprague-Dawley, 250-300 g) were induced by controlled cortical impact. Thirty minutes post-injury, rats received intraperitoneal injection of Phenoxybenzamine HCl (10 mg/kg) dissolved in 0.9% saline. Neurological function was scored at 1, 3, 7 days. Brain tissue was collected at 24 hours to measure water content (edema) and inflammatory cytokines (TNF-α, IL-6) via ELISA [3] |
| Toxicity/Toxicokinetics |
In clinical preoperative applications, phenoxybenzamide hydrochloride (10 mg/day, orally) was well tolerated with only mild adverse reactions, including dizziness (13%), nasal congestion (9%), and orthostatic hypotension (7%); no serious hepatotoxicity or nephrotoxicity was reported [1]. The LD50 of acute intraperitoneal injection of phenoxybenzamide hydrochloride in mice was 85 mg/kg [2]. Intraperitoneal injection of phenoxybenzamide hydrochloride (20 mg/kg/day) in nude mice for 21 consecutive days did not cause significant changes in body weight, liver transaminases (ALT, AST), or renal function indicators (BUN, creatinine) [2]. Phenoxybenzamide hydrochloride has a protein binding rate of 90% in human plasma [1].
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| References |
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| Additional Infomation |
According to an independent committee of scientific and health experts, phenoxybenzylamine hydrochloride may be carcinogenic. Phenoxybenzylamine hydrochloride is a white crystalline powder with a melting point of 137.5-140°C, used as an antihypertensive drug. Phenoxybenzylamine hydrochloride is an organic molecular entity. Phenoxybenzylamine hydrochloride is the hydrochloride form of phenoxybenzylamine, a synthetic diphenylmethylamine alpha-adrenergic antagonist with antihypertensive and vasodilatory effects. Phenoxybenzylamine nonselectively and irreversibly blocks postsynaptic alpha-adrenergic receptors in smooth muscle, thereby preventing vasoconstriction, relieving vasospasm, and reducing peripheral resistance. Reflex tachycardia may occur, and blocking alpha-2 receptors (which enhance norepinephrine release) may exacerbate this tachycardia. Phenoxybenzylamine is likely a human carcinogen. It is a long-duration alpha-adrenergic antagonist. It has been used to treat hypertension and as a peripheral vasodilator. See also: Phenoxybenzylamine (with active moiety). Phenoxybenzylamine hydrochloride is a non-selective, irreversible α-adrenergic receptor antagonist that can form covalent bonds with α1 and α2 receptors[1]. Clinically, it is a first-line drug for the preoperative management of pheochromocytoma, which can control catecholamine-induced hypertension and prevent intraoperative hypertensive crisis[1]. In addition to its α-adrenergic antagonistic effect, phenoxybenzylamine hydrochloride can also exert anti-tumor activity against malignant gliomas by inducing apoptosis and inhibiting proliferation, and exert neuroprotective effects against traumatic brain injury by reducing oxidative stress and inflammation[2,3]. The irreversible binding of the drug to α receptors makes its effect last for a long time (24-48 hours), and it needs to be administered once a day for preoperative preparation[1].
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| Molecular Formula |
C18H23CL2NO
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| Molecular Weight |
340.3
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| Exact Mass |
339.115
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| Elemental Analysis |
C, 63.53; H, 6.81; Cl, 20.84; N, 4.12; O, 4.70
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| CAS # |
63-92-3
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| Related CAS # |
Phenoxybenzamine; 59-96-1; Phenoxybenzamine-d5 hydrochloride; 1329838-45-0; Phenoxybenzamine (benzyl-2,3,4,5,6-d5) (hydrochloride); 1398065-71-8
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| PubChem CID |
5284441
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| Appearance |
White to off-white crystalline powder
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| Boiling Point |
381.5ºC at 760 mmHg
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| Melting Point |
137.5°C
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| Flash Point |
184.5ºC
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| LogP |
4.996
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
22
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| Complexity |
262
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC([H])([H])C([H])([H])N(C([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H])C([H])(C([H])([H])[H])C([H])([H])OC1C([H])=C([H])C([H])=C([H])C=1[H].Cl[H]
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| InChi Key |
VBCPVIWPDJVHAN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H22ClNO.ClH/c1-16(15-21-18-10-6-3-7-11-18)20(13-12-19)14-17-8-4-2-5-9-17;/h2-11,16H,12-15H2,1H3;1H
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| Chemical Name |
N-benzyl-N-(2-chloroethyl)-1-phenoxypropan-2-amine;hydrochloride
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| Synonyms |
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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. |
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| 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: ≥ 2.5 mg/mL (7.35 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 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 (7.35 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 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 (7.35 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 | 2.9386 mL | 14.6929 mL | 29.3858 mL | |
| 5 mM | 0.5877 mL | 2.9386 mL | 5.8772 mL | |
| 10 mM | 0.2939 mL | 1.4693 mL | 2.9386 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 |
| NCT05702944 | Recruiting | Drug: Phenoxybenzamine | Pheochromocytoma Paraganglioma |
Seoul National University Hospital |
January 18, 2023 | Phase 4 |
| NCT01379898 | Completed | Drug: Phenoxybenzamine Drug: Doxazosin |
Pheochromocytoma | University Medical Center Groningen |
December 2011 | Phase 4 |
| NCT00569855 | Completed | Drug: Phenoxybenzamine | Open-heart Surgery Cardiopulmonary Bypass |
University of Arkansas | February 2001 | Phase 2 |
| NCT03176693 | Completed | Drug: Phenoxybenzamine Drug: Doxazosin |
Pheochromocytoma Paraganglioma |
University of California, Los Angeles |
May 5, 2017 | Phase 3 |
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