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Identification
NamePhenoxybenzamine
Accession NumberDB00925  (APRD00651)
Typesmall molecule
Groupsapproved
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
Synonyms
SynonymLanguageCode
FenossibenzaminaNot AvailableDCIT
FenoxibenzaminaSpanishINN
PhenoxybenzaminumLatinINN
POBNot AvailableNot Available
Salts
Name/CAS Structure Properties
Phenoxybenzamine Hydrochloride
Thumb
  • InChI Key: VBCPVIWPDJVHAN-UHFFFAOYNA-N
  • Monoisotopic Mass: 339.115669777
  • Average Mass: 340.287
DBSALT000480
Brand names
NameCompany
DibenzylineWellSpring Pharmaceutical Corporation
Brand mixturesNot Available
Categories
CAS number59-96-1
WeightAverage: 303.826
Monoisotopic: 303.138992038
Chemical FormulaC18H22ClNO
InChI KeyQZVCTJOXCFMACW-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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassPhenol Ethers
Direct parentPhenol Ethers
Alternative parentsAlkyl Aryl Ethers; Tertiary Amines; Polyamines; Alkyl Chlorides; Organochlorides
Substituentsalkyl aryl ether; tertiary amine; ether; polyamine; organochloride; organohalogen; amine; alkyl halide; alkyl chloride; organonitrogen compound
Classification descriptionThis compound belongs to the phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
Pharmacology
IndicationFor the treatment of phaeochromocytoma (malignant), benign prostatic hypertrophy and malignant essential hypertension.
PharmacodynamicsPhenoxybenzamine 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 actionPhenoxybenzamine 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.
AbsorptionTwenty to 30 percent of orally administered phenoxybenzamine appears to be absorbed in the active form.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half life24 hours
ClearanceNot Available
ToxicitySymptoms 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 substrate Non-inhibitor 0.7714
CYP450 2D6 substrate Inhibitor 0.8931
CYP450 2C19 substrate Inhibitor 0.8994
CYP450 3A4 substrate 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
Pharmacoeconomics
Manufacturers
  • Wellspring pharmaceutical corp
Packagers
Dosage forms
FormRouteStrength
CapsuleOral
Prices
Unit descriptionCostUnit
Phenoxybenzamine hcl powd42.35USDg
Dibenzyline 10 mg capsule8.61USDcapsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point39 °CPhysProp
logP4.7Not Available
Predicted Properties
PropertyValueSource
water solubility1.03e-02 g/lALOGPS
logP4.26ALOGPS
logP4.64ChemAxon
logS-4.5ALOGPS
pKa (strongest basic)7.97ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count0ChemAxon
polar surface area12.47ChemAxon
rotatable bond count8ChemAxon
refractivity88.92ChemAxon
polarizability34.09ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  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
  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
External Links
ResourceLink
KEGG CompoundC07435
PubChem Compound4768
PubChem Substance46507191
ChemSpider4604
BindingDB50017679
Therapeutic Targets DatabaseDAP000478
PharmGKBPA450919
RxListhttp://www.rxlist.com/cgi/generic3/phenoxybenz.htm
Drugs.comhttp://www.drugs.com/cdi/phenoxybenzamine.html
WikipediaPhenoxybenzamine
ATC CodesC04AX02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(73.8 KB)
Interactions
Drug Interactions
Drug
TadalafilTadalafil may enhance the hypotensive effect of Phenoxybenzamine. Monitor for hypotension during concomitant therapy.
TamsulosinConcomitant use of alpha1-adrenergic antagonists, Tamsulosin and Phenoxybenzamine, may result in additive antihypertensive effects. Combination therapy is not recommended.
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
VardenafilAdditive hypotensive effects of the PDE5 inhibitor, Vardenafil, and alpha1-blocker, Phenoxybenzamine, may occur. Monitor for hypotension during concomitant therapy.
Food InteractionsNot Available

Targets

1. Alpha-1A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Alpha-1A adrenergic receptor P35348 Details

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
  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
  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
  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
  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

2. Alpha-2A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Alpha-2A adrenergic receptor P08913 Details

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

3. Alpha-2C adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Alpha-2C adrenergic receptor P18825 Details

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

4. Alpha-2B adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Alpha-2B adrenergic receptor P18089 Details

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

5. Calmodulin

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Calmodulin P62158 Details

References:

  1. Cimino M, Weiss B: Characteristics of the binding of phenoxybenzamine to calmodulin. Biochem Pharmacol. 1988 Jul 15;37(14):2739-45. Pubmed
  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
  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
  4. Earl CQ, Prozialeck WC, Weiss B: Interaction of alpha adrenergic antagonists with calmodulin. Life Sci. 1984 Jul 30;35(5):525-34. Pubmed
  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

6. Beta-2 adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Beta-2 adrenergic receptor P07550 Details

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

7. Alpha-1B adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Alpha-1B adrenergic receptor P35368 Details

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

8. Alpha-1D adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Alpha-1D adrenergic receptor P25100 Details

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

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Transporters

1. Solute carrier family 22 member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 2 O15244 Details

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
  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

2. Solute carrier family 22 member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 1 O15245 Details

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

3. Solute carrier family 22 member 3

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 3 O75751 Details

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

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12