Phenoxybenzamine

Targets (8)Transporters (3)Biointeractions (10)

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
Thumb
3D
Similar Structures
Synonyms
  • Fenossibenzamina
  • Fenoxibenzamina
  • Phenoxybenzamine
  • Phenoxybenzaminum
  • POB
Product Ingredients
IngredientUNIICASInChI Key
Phenoxybenzamine HydrochlorideX1IEG24OHL63-92-3VBCPVIWPDJVHAN-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DibenzylineCapsule10 mg/1OralWell Spring Pharmaceutical Corporation1999-10-012017-10-31Us
DibenzylineCapsule10 mg/1OralConcordia Pharmaceuticals Inc.1953-01-26Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Phenoxybenzamine HydrochlorideCapsule10 mg/1OralWest-Ward Pharmaceuticals Corp.2015-08-10Not applicableUs
Phenoxybenzamine HydrochlorideCapsule10 mg/1OralPar Pharmaceutical2017-01-24Not applicableUs
Phenoxybenzamine HydrochlorideCapsule10 mg/1OralPrasco, Laboratories2015-08-11Not applicableUs
International/Other Brands
Dibenzyline
Categories
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

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.

TargetActionsOrganism
AAlpha-1A adrenergic receptor
antagonist
Human
AAlpha-2A adrenergic receptor
antagonist
Human
UAlpha-2C adrenergic receptor
antagonist
Human
UAlpha-2B adrenergic receptor
antagonist
Human
UCalmodulin
inhibitor
Human
UBeta-2 adrenergic receptorNot AvailableHuman
UAlpha-1B adrenergic receptor
antagonist
Human
UAlpha-1D adrenergic receptor
antagonist
Human
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
DrugInteraction
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidPhenoxybenzamine may increase the hypotensive activities of 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
1-benzylimidazoleThe risk or severity of hypertension can be increased when Phenoxybenzamine is combined with 1-benzylimidazole.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of hypertension can be increased when Phenoxybenzamine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of hypertension can be increased when Phenoxybenzamine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of hypertension can be increased when Phenoxybenzamine is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of hypertension can be increased when Phenoxybenzamine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe therapeutic efficacy of 4-Methoxyamphetamine can be decreased when used in combination with Phenoxybenzamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of hypertension can be increased when Phenoxybenzamine is combined with 5-methoxy-N,N-dimethyltryptamine.
AbediterolThe therapeutic efficacy of Abediterol can be decreased when used in combination with Phenoxybenzamine.
AcebutololAcebutolol may increase the orthostatic hypotensive activities of Phenoxybenzamine.
Food Interactions
Not Available

References

General References
  1. 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]
  2. 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
PhaseStatusPurposeConditionsCount
2CompletedTreatmentCardiopulmonary Bypass / Open-heart Surgery1
2Unknown StatusTreatmentCongenital Heart Disease (CHD)1
3RecruitingTreatmentParaganglioma / Pheochromocytomas1
4CompletedTreatmentPheochromocytomas1
Not AvailableTerminatedTreatmentCardiopulmonary Bypass / Congenital Heart Surgery1

Pharmacoeconomics

Manufacturers
  • Wellspring pharmaceutical corp
Packagers
  • Gallipot
  • Murfreesboro Pharmaceutical Nursing Supply
  • Wellspring Pharmaceutical
Dosage forms
FormRouteStrength
CapsuleOral10 mg/1
Prices
Unit descriptionCostUnit
Phenoxybenzamine hcl powd42.35USD g
Dibenzyline 10 mg capsule8.61USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)39 °CPhysProp
logP4.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0103 mg/mLALOGPS
logP4.26ALOGPS
logP4.64ChemAxon
logS-4.5ALOGPS
pKa (Strongest Basic)7.97ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area12.47 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity88.92 m3·mol-1ChemAxon
Polarizability34.09 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9629
Caco-2 permeable+0.7367
P-glycoprotein substrateSubstrate0.6059
P-glycoprotein inhibitor IInhibitor0.6043
P-glycoprotein inhibitor IIInhibitor0.5871
Renal organic cation transporterInhibitor0.7955
CYP450 2C9 substrateNon-substrate0.6666
CYP450 2D6 substrateNon-substrate0.6013
CYP450 3A4 substrateSubstrate0.5937
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.7714
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6682
Ames testAMES toxic0.9107
CarcinogenicityNon-carcinogens0.7565
BiodegradationNot ready biodegradable0.9973
Rat acute toxicity2.1163 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.7145
hERG inhibition (predictor II)Inhibitor0.5874
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot 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

Details1. Alpha-1A adrenergic receptor
Kind
Protein
Organism
Human
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
  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
Details2. Alpha-2A adrenergic receptor
Kind
Protein
Organism
Human
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
  1. 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]
Details3. Alpha-2C adrenergic receptor
Kind
Protein
Organism
Human
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
  1. 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]
Details4. Alpha-2B adrenergic receptor
Kind
Protein
Organism
Human
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
  1. 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]
Details5. Calmodulin
Kind
Protein
Organism
Human
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
  1. Cimino M, Weiss B: Characteristics of the binding of phenoxybenzamine to calmodulin. Biochem Pharmacol. 1988 Jul 15;37(14):2739-45. [PubMed:3134891]
  2. 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]
  3. 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]
  4. Earl CQ, Prozialeck WC, Weiss B: Interaction of alpha adrenergic antagonists with calmodulin. Life Sci. 1984 Jul 30;35(5):525-34. [PubMed:6146911]
  5. 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]
Details6. Beta-2 adrenergic receptor
Kind
Protein
Organism
Human
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
  1. 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]
Details7. Alpha-1B adrenergic receptor
Kind
Protein
Organism
Human
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
  1. 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]
Details8. Alpha-1D adrenergic receptor
Kind
Protein
Organism
Human
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
  1. 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

Details1. Solute carrier family 22 member 2
Kind
Protein
Organism
Human
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
  1. 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]
  2. 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]
Details2. Solute carrier family 22 member 1
Kind
Protein
Organism
Human
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
  1. 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]
Details3. Solute carrier family 22 member 3
Kind
Protein
Organism
Human
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
  1. 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 December 14, 2018 16:26