Synonym
Phenoxybenzamine hydrochloride, Phenoxybenzamine, Phenoxybenzamine HCl, Dibenzyline, NCI-C01661, NCI C01661, NCIC01661
IUPAC/Chemical Name
N-benzyl-N-(2-chloroethyl)-1-phenoxypropan-2-amine hydrochloride
InChi Key
VBCPVIWPDJVHAN-UHFFFAOYSA-N
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
SMILES Code
CC(N(CCCl)CC1=CC=CC=C1)COC2=CC=CC=C2.[H]Cl
Appearance
White to off-white crystalline powder.
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Phenoxybenzamine hydrochloride is a nonselective, irreversible, orally active α-adrenoceptor antagonist.
In vitro activity:
Inhibitory effects on human tumor cell cultures are also reported in the present study. Phenoxybenzamine was also found to have histone deacetylase inhibitory activity; histone deacetylase isoforms 5, 6, and 9 were the most sensitive to inhibition by phenoxybenzamine. The importance of elevated levels of these isoforms as biomarkers of poor prognosis in human malignant disease, and the recognized suppression of tumor growth that may accrue from their inhibition, opens consideration of possible translation of phenoxybenzamine to new clinical applications.
Reference: PLoS One. 2018 Jun 13;13(6):e0198514. https://pubmed.ncbi.nlm.nih.gov/29897996/
In vivo activity:
This study further tested phenoxybenzamine in the rat lateral fluid percussion model of TBI. When administered 8 h after TBI, phenoxybenzamine improved neurological severity scoring and foot fault assessments. At 25 days post injury, phenoxybenzamine treated TBI animals also showed a significant improvement in both learning and memory compared to saline treated controls. This study further examined gene expression changes within the cortex following TBI. At 32 h post-TBI phenoxybenzamine treated animals had significantly lower expression of pro-inflammatory signaling proteins CCL2, IL1β, and MyD88, suggesting that phenoxybenzamine may exert a neuroprotective effect by reducing neuroinflammation after TBI.
Reference: Int J Mol Sci. 2014 Jan 20;15(1):1402-17. https://pubmed.ncbi.nlm.nih.gov/24447929/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMF |
30.0 |
88.16 |
|
| DMF:PBS (pH 7.2) (1:2) |
0.3 |
0.88 |
|
| DMSO |
64.3 |
189.06 |
|
| Ethanol |
46.5 |
136.65 |
|
| Water |
8.8 |
25.96 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
340.29
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Inchiosa MA Jr. Anti-tumor activity of phenoxybenzamine and its inhibition of histone deacetylases. PLoS One. 2018 Jun 13;13(6):e0198514. doi: 10.1371/journal.pone.0198514. PMID: 29897996; PMCID: PMC5999115.
2. Lin XB, Jiang L, Ding MH, Chen ZH, Bao Y, Chen Y, Sun W, Zhang CR, Hu HK, Cai Z, Lu CY, Zhou JY, Qian J, Wu XJ, Jin WL, Hu GH. Anti-tumor activity of phenoxybenzamine hydrochloride on malignant glioma cells. Tumour Biol. 2016 Mar;37(3):2901-8. doi: 10.1007/s13277-015-4102-y. Epub 2015 Sep 26. PMID: 26409450.
3. Rau TF, Kothiwal A, Rova A, Rhoderick JF, Poulsen DJ. Phenoxybenzamine is neuroprotective in a rat model of severe traumatic brain injury. Int J Mol Sci. 2014 Jan 20;15(1):1402-17. doi: 10.3390/ijms15011402. PMID: 24447929; PMCID: PMC3907876.
4. Chang M, Smith S, Thorpe A, Barratt MJ, Karim F. Evaluation of phenoxybenzamine in the CFA model of pain following gene expression studies and connectivity mapping. Mol Pain. 2010 Sep 16;6:56. doi: 10.1186/1744-8069-6-56. PMID: 20846436; PMCID: PMC2949723.
In vitro protocol:
1. Inchiosa MA Jr. Anti-tumor activity of phenoxybenzamine and its inhibition of histone deacetylases. PLoS One. 2018 Jun 13;13(6):e0198514. doi: 10.1371/journal.pone.0198514. PMID: 29897996; PMCID: PMC5999115.
2. Lin XB, Jiang L, Ding MH, Chen ZH, Bao Y, Chen Y, Sun W, Zhang CR, Hu HK, Cai Z, Lu CY, Zhou JY, Qian J, Wu XJ, Jin WL, Hu GH. Anti-tumor activity of phenoxybenzamine hydrochloride on malignant glioma cells. Tumour Biol. 2016 Mar;37(3):2901-8. doi: 10.1007/s13277-015-4102-y. Epub 2015 Sep 26. PMID: 26409450.
In vivo protocol:
1. Rau TF, Kothiwal A, Rova A, Rhoderick JF, Poulsen DJ. Phenoxybenzamine is neuroprotective in a rat model of severe traumatic brain injury. Int J Mol Sci. 2014 Jan 20;15(1):1402-17. doi: 10.3390/ijms15011402. PMID: 24447929; PMCID: PMC3907876.
2. Chang M, Smith S, Thorpe A, Barratt MJ, Karim F. Evaluation of phenoxybenzamine in the CFA model of pain following gene expression studies and connectivity mapping. Mol Pain. 2010 Sep 16;6:56. doi: 10.1186/1744-8069-6-56. PMID: 20846436; PMCID: PMC2949723.
1: van der Zee PA, de Boer A. Pheochromocytoma: a review on preoperative treatment with phenoxybenzamine or doxazosin. Neth J Med. 2014 May;72(4):190-201. Review. PubMed PMID: 24829175.
2: National Toxicology Program. Phenoxybenzamine hydrochloride. Rep Carcinog. 2011;12:344-5. PubMed PMID: 21863081.
3: Rau TF, Kothiwal A, Rova A, Rhoderick JF, Poulsen DJ. Phenoxybenzamine is neuroprotective in a rat model of severe traumatic brain injury. Int J Mol Sci. 2014 Jan 20;15(1):1402-17. doi: 10.3390/ijms15011402. PubMed PMID: 24447929; PubMed Central PMCID: PMC3907876.
4: Lin XB, Jiang L, Ding MH, Chen ZH, Bao Y, Chen Y, Sun W, Zhang CR, Hu HK, Cai Z, Lu CY, Zhou JY, Qian J, Wu XJ, Jin WL, Hu GH. Anti-tumor activity of phenoxybenzamine hydrochloride on malignant glioma cells. Tumour Biol. 2016 Mar;37(3):2901-8. doi: 10.1007/s13277-015-4102-y. Epub 2015 Sep 26. PubMed PMID: 26409450.
5: Lim LY, Tan LL, Chan EW, Yow KL, Chan SY, Ho PC. Stability of phenoxybenzamine hydrochloride in various vehicles. Am J Health Syst Pharm. 1997 Sep 15;54(18):2073-8. PubMed PMID: 9377206.
6: Phenoxybenzamine and phenoxybenzamine hydrochloride. IARC Monogr Eval Carcinog Risk Chem Hum. 1980;24:185-94. Review. PubMed PMID: 7009392.
7: Sambhunath D, Pankaj K, Usha K. Role of phenoxybenzamine in perioperative clinical practice. Ann Card Anaesth. 2015 Oct-Dec;18(4):577-8. doi: 10.4103/0971-9784.166473. PubMed PMID: 26440247; PubMed Central PMCID: PMC4881667.
8: Phenoxybenzamine hydrochloride. Rep Carcinog. 2004;11:III216. PubMed PMID: 21089945.
9: National Toxicology Program. Phenoxybenzamine hydrochloride. Rep Carcinog. 2002;10:197-8. Update in: Rep Carcinog. 2004;11:III216. PubMed PMID: 15332291.
10: Agrawal R, Mishra SK, Bhatia E, Mishra A, Chand G, Agarwal G, Agarwal A, Verma AK. Prospective study to compare peri-operative hemodynamic alterations following preparation for pheochromocytoma surgery by phenoxybenzamine or prazosin. World J Surg. 2014 Mar;38(3):716-23. PubMed PMID: 24233658.
11: Khanna OP, Gonick P. Effects of phenoxybenzamine hydrochloride on canine lower urinary tract: clinical implications. Urology. 1975 Sep;6(3):323-30. PubMed PMID: 1167189.
12: Phenoxybenzamine (hydrochloride). IARC Monogr Eval Carcinog Risk Chem Man. 1975;9:223-8. Review. PubMed PMID: 791836.
13: Ramachandran R, Rewari V. Preoperative optimization in pheochromocytoma: phenoxybenzamine may be redundant but not alpha blockade. Can J Anaesth. 2016 May;63(5):629. doi: 10.1007/s12630-015-0557-y. Epub 2015 Dec 7. PubMed PMID: 26643509.
14: Portoghese PS, Riley TN, Miller JW. Stereochemical studies on medicinal agents. 10. The role of chirality in alpha-adrenergic receptor blockage by (plus)-and(minus)-phenoxybenzamine hydrochloride. J Med Chem. 1971 Jul;14(17):561-4. PubMed PMID: 4151883.
15: Sharma PL. Comparative effect of prophylactic administration of isoxsuprine hydrochloride and phenoxybenzamine hydrochloride on the survival rate of dogs subjected to acute blood loss. Indian J Med Res. 1969 Oct;57(10):1902-10. PubMed PMID: 5372176.
16: Collado Mdel C, Nedergaard M. [On the stability of phenoxybenzamine hydrochloride in solution]. Ann Pharm Fr. 1968 May;26(5):409-12. French. PubMed PMID: 5708743.
17: Mitchell JC, Maibach HI. Allergic contact dermatitis from phenoxybenzamine hydrochloride: cross-sensitivity to some related haloalkylamine compounds. Contact Dermatitis. 1975 Dec;1(6):363-6. PubMed PMID: 1235295.
18: Dunzendorfer U. alpha-Difluoromethylornithine (alpha DFMO) and phenoxybenzamine hydrochloride in the treatment of chronic non-suppurative prostatitis. Arzneimittelforschung. 1981;31(2):382-5. PubMed PMID: 6784733.
19: Cimino M, Weiss B. Characteristics of the binding of phenoxybenzamine to calmodulin. Biochem Pharmacol. 1988 Jul 15;37(14):2739-45. PubMed PMID: 3134891.
20: Lewis JE, Miller JW. The synthesis of tritium-labeled phenoxybenzamine hydrochloride. J Med Chem. 1966 Mar;9(2):261-2. PubMed PMID: 5911816.
