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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyPhenoxybenzamine
Identification
- Name
- Phenoxybenzamine
- Accession Number
- DB00925 (APRD00651)
- Type
- Small Molecule
- Groups
- Approved
- Description
An alpha-adrenergic antagonist with long duration of action. It has been used to treat hypertension and as a peripheral vasodilator. [PubChem]
- Structure
Structure for Phenoxybenzamine (DB00925)
- Synonyms
- Fenossibenzamina
- Fenoxibenzamina
- Phenoxybenzamine
- Phenoxybenzaminum
- POB
- Product Ingredients
Ingredient UNII CAS InChI Key Phenoxybenzamine Hydrochloride X1IEG24OHL 63-92-3 VBCPVIWPDJVHAN-UHFFFAOYSA-N - Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Dibenzyline Capsule 10 mg/1 Oral Concordia Pharmaceuticals Inc. 1953-01-26 Not applicable US 
Dibenzyline Capsule 10 mg/1 Oral Well Spring Pharmaceutical Corporation 1999-10-01 2017-10-31 US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Phenoxybenzamine Hydrochloride Capsule 10 mg/1 Oral Par Pharmaceutical 2017-01-24 Not applicable US Phenoxybenzamine Hydrochloride Capsule 10 mg/1 Oral West-Ward Pharmaceuticals Corp. 2015-08-10 Not applicable US Phenoxybenzamine Hydrochloride Capsule 10 mg/1 Oral Prasco Laboratories 2015-08-11 Not applicable US - Categories
- Adrenergic Agents
- Adrenergic alpha-1 Receptor Antagonists
- Adrenergic alpha-Antagonists
- Adrenergic Antagonists
- Agents that produce hypertension
- Amines
- Antihypertensive Agents
- Cardiovascular Agents
- Ethylamines
- Hypotensive Agents
- Neurotransmitter Agents
- OCT1 inhibitors
- OCT2 Inhibitors
- Peripheral alpha-1 blockers
- Peripheral Vasodilators
- Vasodilating Agents
- UNII
- 0TTZ664R7Z
- CAS number
- 59-96-1
- Weight
- Average: 303.826
Monoisotopic: 303.138992038 - Chemical Formula
- C18H22ClNO
- InChI Key
- QZVCTJOXCFMACW-UHFFFAOYSA-N
- InChI
- InChI=1S/C18H22ClNO/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
- IUPAC Name
- benzyl(2-chloroethyl)(1-phenoxypropan-2-yl)amine
- SMILES
- CC(COC1=CC=CC=C1)N(CCCl)CC1=CC=CC=C1
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Pharmacology
- Indication
For the treatment of phaeochromocytoma (malignant), benign prostatic hypertrophy and malignant essential hypertension.
- Associated Conditions
- Pharmacodynamics
Phenoxybenzamine is indicated for the control of episodes of hypertension and sweating that occur with a disease called pheochromocytoma. If tachycardia is excessive, it may be necessary to use a beta-blocking agent concomitantly. Phenoxybenzamine is a long-acting, adrenergic, alpha-receptor blocking agent which can produce and maintain "chemical sympathectomy" by oral administration. It increases blood flow to the skin, mucosa and abdominal viscera, and lowers both supine and erect blood pressures. It has no effect on the parasympathetic system. Phenoxybenzamine works by blocking alpha receptors in certain parts of the body. Alpha receptors are present in the muscle that lines the walls of blood vessels. When the receptors are blocked by Phenoxybenzamine, the muscle relaxes and the blood vessels widen. This widening of the blood vessels results in a lowering of blood pressure.
- Mechanism of action
Phenoxybenzamine produces its therapeutic actions by blocking alpha receptors, leading to a muscle relaxation and a widening of the blood vessels. This widening of the blood vessels results in a lowering of blood pressure.
Target Actions Organism AAlpha-1A adrenergic receptor antagonistHumans AAlpha-2A adrenergic receptor antagonistHumans UAlpha-2C adrenergic receptor antagonistHumans UAlpha-2B adrenergic receptor antagonistHumans UCalmodulin inhibitorHumans UBeta-2 adrenergic receptor Not Available Humans UAlpha-1B adrenergic receptor antagonistHumans UAlpha-1D adrenergic receptor antagonistHumans - Absorption
Twenty to 30 percent of orally administered phenoxybenzamine appears to be absorbed in the active form.
- Volume of distribution
- Not Available
- Protein binding
- Not Available
- Metabolism
- Not Available
- Route of elimination
- Not Available
- Half life
24 hours
- Clearance
- Not Available
- Toxicity
Symptoms of overdose are largely the result of block of the sympathetic nervous system and of the circulating epinephrine. They may include postural hypotension resulting in dizziness or fainting, tachycardia, particularly postural, vomiting; lethargy, and shock.
- Affected organisms
- Humans and other mammals
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid The therapeutic efficacy of 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid can be increased when used in combination with Phenoxybenzamine. 1-benzylimidazole The risk or severity of hypertension can be increased when Phenoxybenzamine is combined with 1-benzylimidazole. 2,5-Dimethoxy-4-ethylamphetamine The therapeutic efficacy of Phenoxybenzamine can be decreased when used in combination with 2,5-Dimethoxy-4-ethylamphetamine. 2,5-Dimethoxy-4-ethylthioamphetamine The therapeutic efficacy of Phenoxybenzamine can be decreased when used in combination with 2,5-Dimethoxy-4-ethylthioamphetamine. 4-Bromo-2,5-dimethoxyamphetamine The therapeutic efficacy of Phenoxybenzamine can be decreased when used in combination with 4-Bromo-2,5-dimethoxyamphetamine. 4-Methoxyamphetamine The therapeutic efficacy of 4-Methoxyamphetamine can be decreased when used in combination with Phenoxybenzamine. 5-methoxy-N,N-dimethyltryptamine The risk or severity of hypertension can be increased when Phenoxybenzamine is combined with 5-methoxy-N,N-dimethyltryptamine. 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypotensive activities of Phenoxybenzamine. Abediterol The therapeutic efficacy of Abediterol can be decreased when used in combination with Phenoxybenzamine. Acebutolol Acebutolol may increase the orthostatic hypotensive activities of Phenoxybenzamine. - Food Interactions
- Not Available
References
- General References
- Caine M, Perlberg S, Meretyk S: A placebo-controlled double-blind study of the effect of phenoxybenzamine in benign prostatic obstruction. Br J Urol. 1978 Dec;50(7):551-4. [PubMed:88984]
- Frang H, Cockcroft V, Karskela T, Scheinin M, Marjamaki A: Phenoxybenzamine binding reveals the helical orientation of the third transmembrane domain of adrenergic receptors. J Biol Chem. 2001 Aug 17;276(33):31279-84. Epub 2001 Jun 6. [PubMed:11395517]
- External Links
- Human Metabolome Database
- HMDB0015061
- KEGG Compound
- C07435
- PubChem Compound
- 4768
- PubChem Substance
- 46507191
- ChemSpider
- 4604
- BindingDB
- 50017679
- ChEBI
- 8077
- ChEMBL
- CHEMBL753
- Therapeutic Targets Database
- DAP000478
- PharmGKB
- PA450919
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Phenoxybenzamine
- ATC Codes
- C04AX02 — Phenoxybenzamine
- MSDS
- Download (73.8 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Completed Treatment Cardiopulmonary Bypass / Open-heart Surgery 1 2 Unknown Status Treatment Congenital Heart Disease (CHD) 1 3 Recruiting Treatment Paraganglioma / Pheochromocytomas 1 4 Completed Treatment Pheochromocytomas 1 Not Available Terminated Treatment Cardiopulmonary Bypass / Congenital Heart Surgery 1
Pharmacoeconomics
- Manufacturers
- Wellspring pharmaceutical corp
- Packagers
- Gallipot
- Murfreesboro Pharmaceutical Nursing Supply
- Wellspring Pharmaceutical
- Dosage forms
Form Route Strength Capsule Oral 10 mg/1 - Prices
Unit description Cost Unit Phenoxybenzamine hcl powd 42.35USD g Dibenzyline 10 mg capsule 8.61USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 39 °C PhysProp logP 4.7 Not Available - Predicted Properties
Property Value Source Water Solubility 0.0103 mg/mL ALOGPS logP 4.26 ALOGPS logP 4.64 ChemAxon logS -4.5 ALOGPS pKa (Strongest Basic) 7.97 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 2 ChemAxon Hydrogen Donor Count 0 ChemAxon Polar Surface Area 12.47 Å2 ChemAxon Rotatable Bond Count 8 ChemAxon Refractivity 88.92 m3·mol-1 ChemAxon Polarizability 34.09 Å3 ChemAxon Number of Rings 2 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule Yes ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9629 Caco-2 permeable + 0.7367 P-glycoprotein substrate Substrate 0.6059 P-glycoprotein inhibitor I Inhibitor 0.6043 P-glycoprotein inhibitor II Inhibitor 0.5871 Renal organic cation transporter Inhibitor 0.7955 CYP450 2C9 substrate Non-substrate 0.6666 CYP450 2D6 substrate Non-substrate 0.6013 CYP450 3A4 substrate Substrate 0.5937 CYP450 1A2 substrate Inhibitor 0.9107 CYP450 2C9 inhibitor Non-inhibitor 0.7714 CYP450 2D6 inhibitor Inhibitor 0.8931 CYP450 2C19 inhibitor Inhibitor 0.8994 CYP450 3A4 inhibitor Non-inhibitor 0.8309 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6682 Ames test AMES toxic 0.9107 Carcinogenicity Non-carcinogens 0.7565 Biodegradation Not ready biodegradable 0.9973 Rat acute toxicity 2.1163 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.7145 hERG inhibition (predictor II) Inhibitor 0.5874
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Taxonomy
- Description
- This compound belongs to the class of organic compounds known as phenylmethylamines. These are compounds containing a phenylmethtylamine moiety, which consists of a phenyl group substituted by an methanamine.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Phenylmethylamines
- Direct Parent
- Phenylmethylamines
- Alternative Parents
- Phenoxy compounds / Phenol ethers / Benzylamines / Aralkylamines / Alkyl aryl ethers / Trialkylamines / Organopnictogen compounds / Organochlorides / Hydrocarbon derivatives / Alkyl chlorides
- Substituents
- Benzylamine / Phenoxy compound / Phenol ether / Phenylmethylamine / Alkyl aryl ether / Aralkylamine / Tertiary aliphatic amine / Tertiary amine / Ether / Organopnictogen compound
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- aromatic amine (CHEBI:8077)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Protein heterodimerization activity
- Specific Function
- This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
- Gene Name
- ADRA1A
- Uniprot ID
- P35348
- Uniprot Name
- Alpha-1A adrenergic receptor
- Molecular Weight
- 51486.005 Da
References
- Stam WB, Van der Graaf PH, Saxena PR: Analysis of alpha 1L-adrenoceptor pharmacology in rat small mesenteric artery. Br J Pharmacol. 1999 Jun;127(3):661-70. [PubMed:10401556]
- Michel MC, Hanft G, Gross G: Functional studies on alpha 1-adrenoceptor subtypes mediating inotropic effects in rat right ventricle. Br J Pharmacol. 1994 Feb;111(2):539-46. [PubMed:7911719]
- Yu Y, Koss MC: Functional characterization of alpha-adrenoceptors mediating pupillary dilation in rats. Eur J Pharmacol. 2003 Jun 20;471(2):135-40. [PubMed:12818701]
- Salles J, Gascon S, Badia A: Sustained increase in rat myocardial alpha 1A-adrenoceptors induced by 6-hydroxydopamine treatment involves a decelerated receptor turnover. Naunyn Schmiedebergs Arch Pharmacol. 1996 Mar;353(4):408-16. [PubMed:8935707]
- Suzuki E, Tsujimoto G, Tamura K, Hashimoto K: Two pharmacologically distinct alpha 1-adrenoceptor subtypes in the contraction of rabbit aorta: each subtype couples with a different Ca2+ signalling mechanism and plays a different physiological role. Mol Pharmacol. 1990 Nov;38(5):725-36. [PubMed:1978244]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Thioesterase binding
- Specific Function
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
- Gene Name
- ADRA2A
- Uniprot ID
- P08913
- Uniprot Name
- Alpha-2A adrenergic receptor
- Molecular Weight
- 48956.275 Da
References
- Frang H, Cockcroft V, Karskela T, Scheinin M, Marjamaki A: Phenoxybenzamine binding reveals the helical orientation of the third transmembrane domain of adrenergic receptors. J Biol Chem. 2001 Aug 17;276(33):31279-84. Epub 2001 Jun 6. [PubMed:11395517]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Protein homodimerization activity
- Specific Function
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
- Gene Name
- ADRA2C
- Uniprot ID
- P18825
- Uniprot Name
- Alpha-2C adrenergic receptor
- Molecular Weight
- 49521.585 Da
References
- Frang H, Cockcroft V, Karskela T, Scheinin M, Marjamaki A: Phenoxybenzamine binding reveals the helical orientation of the third transmembrane domain of adrenergic receptors. J Biol Chem. 2001 Aug 17;276(33):31279-84. Epub 2001 Jun 6. [PubMed:11395517]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Epinephrine binding
- Specific Function
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine...
- Gene Name
- ADRA2B
- Uniprot ID
- P18089
- Uniprot Name
- Alpha-2B adrenergic receptor
- Molecular Weight
- 49565.8 Da
References
- Frang H, Cockcroft V, Karskela T, Scheinin M, Marjamaki A: Phenoxybenzamine binding reveals the helical orientation of the third transmembrane domain of adrenergic receptors. J Biol Chem. 2001 Aug 17;276(33):31279-84. Epub 2001 Jun 6. [PubMed:11395517]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Titin binding
- Specific Function
- Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number...
- Gene Name
- CALM1
- Uniprot ID
- P0DP23
- Uniprot Name
- Calmodulin
- Molecular Weight
- 16837.47 Da
References
- Cimino M, Weiss B: Characteristics of the binding of phenoxybenzamine to calmodulin. Biochem Pharmacol. 1988 Jul 15;37(14):2739-45. [PubMed:3134891]
- Suko J, Wyskovsky W, Pidlich J, Hauptner R, Plank B, Hellmann G: Calcium release from calmodulin and its C-terminal or N-terminal halves in the presence of the calmodulin antagonists phenoxybenzamine and melittin measured by stopped-flow fluorescence with Quin 2 and intrinsic tyrosine. Inhibition of calmodulin-dependent protein kinase of cardiac sarcoplasmic reticulum. Eur J Biochem. 1986 Sep 15;159(3):425-34. [PubMed:3758070]
- Lukas TJ, Marshak DR, Watterson DM: Drug-protein interactions: isolation and characterization of covalent adducts of phenoxybenzamine and calmodulin. Biochemistry. 1985 Jan 1;24(1):151-7. [PubMed:3994963]
- Earl CQ, Prozialeck WC, Weiss B: Interaction of alpha adrenergic antagonists with calmodulin. Life Sci. 1984 Jul 30;35(5):525-34. [PubMed:6146911]
- Kuromi H, Yoshihara M, Kidokoro Y: An inhibitory role of calcineurin in endocytosis of synaptic vesicles at nerve terminals of Drosophila larvae. Neurosci Res. 1997 Feb;27(2):101-13. [PubMed:9100252]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Protein homodimerization activity
- Specific Function
- Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately ...
- Gene Name
- ADRB2
- Uniprot ID
- P07550
- Uniprot Name
- Beta-2 adrenergic receptor
- Molecular Weight
- 46458.32 Da
References
- Frang H, Cockcroft V, Karskela T, Scheinin M, Marjamaki A: Phenoxybenzamine binding reveals the helical orientation of the third transmembrane domain of adrenergic receptors. J Biol Chem. 2001 Aug 17;276(33):31279-84. Epub 2001 Jun 6. [PubMed:11395517]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Protein heterodimerization activity
- Specific Function
- This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
- Gene Name
- ADRA1B
- Uniprot ID
- P35368
- Uniprot Name
- Alpha-1B adrenergic receptor
- Molecular Weight
- 56835.375 Da
References
- Minneman KP, Theroux TL, Hollinger S, Han C, Esbenshade TA: Selectivity of agonists for cloned alpha 1-adrenergic receptor subtypes. Mol Pharmacol. 1994 Nov;46(5):929-36. [PubMed:7969082]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Alpha1-adrenergic receptor activity
- Specific Function
- This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
- Gene Name
- ADRA1D
- Uniprot ID
- P25100
- Uniprot Name
- Alpha-1D adrenergic receptor
- Molecular Weight
- 60462.205 Da
References
- Minneman KP, Theroux TL, Hollinger S, Han C, Esbenshade TA: Selectivity of agonists for cloned alpha 1-adrenergic receptor subtypes. Mol Pharmacol. 1994 Nov;46(5):929-36. [PubMed:7969082]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Quaternary ammonium group transmembrane transporter activity
- Specific Function
- Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
- Gene Name
- SLC22A2
- Uniprot ID
- O15244
- Uniprot Name
- Solute carrier family 22 member 2
- Molecular Weight
- 62579.99 Da
References
- Hayer-Zillgen M, Bruss M, Bonisch H: Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3. Br J Pharmacol. 2002 Jul;136(6):829-36. [PubMed:12110607]
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Secondary active organic cation transmembrane transporter activity
- Specific Function
- Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
- Gene Name
- SLC22A1
- Uniprot ID
- O15245
- Uniprot Name
- Solute carrier family 22 member 1
- Molecular Weight
- 61153.345 Da
References
- Hayer-Zillgen M, Bruss M, Bonisch H: Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3. Br J Pharmacol. 2002 Jul;136(6):829-36. [PubMed:12110607]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Toxin transporter activity
- Specific Function
- Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain.
- Gene Name
- SLC22A3
- Uniprot ID
- O75751
- Uniprot Name
- Solute carrier family 22 member 3
- Molecular Weight
- 61279.485 Da
References
- Hayer-Zillgen M, Bruss M, Bonisch H: Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3. Br J Pharmacol. 2002 Jul;136(6):829-36. [PubMed:12110607]
Drug created on June 13, 2005 07:24 / Updated on April 10, 2019 22:38