Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Dibenzyline	Capsule	10 mg/1	Oral	Concordia Pharmaceuticals Inc.	1953-01-26	Not applicable
Dibenzyline	Capsule	10 mg/1	Oral	Well Spring Pharmaceutical Corporation	1999-10-01	2017-10-31

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
Phenoxybenzamine Hydrochloride	Capsule	10 mg/1	Oral	Prasco Laboratories	2015-08-11	Not applicable
Phenoxybenzamine Hydrochloride	Capsule	10 mg/1	Oral	West-Ward Pharmaceuticals Corp.	2015-08-10	Not applicable

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.

Target	Actions	Organism
AAlpha-1A adrenergic receptor	antagonist	Humans
AAlpha-2A adrenergic receptor	antagonist	Humans
UAlpha-2C adrenergic receptor	antagonist	Humans
UAlpha-2B adrenergic receptor	antagonist	Humans
UCalmodulin	inhibitor	Humans
UBeta-2 adrenergic receptor	Not Available	Humans
UAlpha-1B adrenergic receptor	antagonist	Humans
UAlpha-1D adrenergic receptor	antagonist	Humans

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	Phenoxybenzamine may increase the hypotensive activities of 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
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.
3,4-Methylenedioxyamphetamine	The therapeutic efficacy of Phenoxybenzamine can be decreased when used in combination with 3,4-Methylenedioxyamphetamine.
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.
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

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

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

Details1. Alpha-1A adrenergic receptor

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]

Details2. Alpha-2A adrenergic receptor

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]

Details3. Alpha-2C adrenergic receptor

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]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	3.5	N/A	N/A	2172775

Details4. Alpha-2B adrenergic receptor

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]

Details5. Calmodulin

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]

Details6. Beta-2 adrenergic receptor

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]

Details7. Alpha-1B adrenergic receptor

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]

Details8. Alpha-1D adrenergic receptor

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

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	4900	N/A	N/A	12110607

Details1. Solute carrier family 22 member 2

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]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	15100	N/A	N/A	18788725
IC 50 (nM)	2720	N/A	N/A	12110607

Details2. Solute carrier family 22 member 1

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]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	6130	N/A	N/A	12110607

Details3. Solute carrier family 22 member 3

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 December 16, 2018 06:44

Phenoxybenzamine

Identification

Structure for Phenoxybenzamine (DB00925)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

References

References

References

References

References

References

References

Transporters

References

References

References