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This repository is under review for potential modification in compliance with Administration directives.

Details

Stereochemistry RACEMIC
Molecular Formula C18H22ClNO
Molecular Weight 303.826
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PHENOXYBENZAMINE

SMILES

CC(COC1=CC=CC=C1)N(CCCl)CC2=CC=CC=C2

InChI

InChIKey=QZVCTJOXCFMACW-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Molecular Formula C18H22ClNO
Molecular Weight 303.826
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/11395517

Phenoxybenzamin (marketed under the trade name Dibenzyline) is an alpha-adrenergic antagonist with long duration of action. It is indicated in the treatment of pheochromocytoma, to control episodes of hypertension and sweating. If tachycardia is excessive, it may be necessary to use a beta-blocking agent concomitantly. 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. Phenoxybenzamine hydrochloride 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. Twenty to percent of orally administered phenoxybenzamine appears to be absorbed in the active form. The half-life of orally administered phenoxybenzamine hydrochloride is not known; however, the half-life of intravenously administered drug is approximately 24 hours. Demonstrable effects with intravenous administration persist for at least 3 to 4 days, and the effects of daily administration are cumulative for nearly a week. The following adverse reactions have been observed, but there are insufficient data to support an estimate of their frequency: Postural hypotension, tachycardia, inhibition of ejaculation, nasal congestion, and miosis. These so-called “side effects” are actually evidence of adrenergic blockade and vary according to the degree of blockade. Miscellaneous: Gastrointestinal irritation, drowsiness, fatigue.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
DIBENZYLINE

Approved Use

INDICATION AND USAGE Phenoxybenzamine hydrochloride is indicated in the treatment of pheochromocytoma, to control episodes of hypertension and sweating. If tachycardia is excessive, it may be necessary to use a beta-blocking agent concomitantly.

Launch Date

1953
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3332.3 pg/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PHENOXYBENZAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
3746.5 pg × h/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PHENOXYBENZAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.54 h
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PHENOXYBENZAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
40 mg 3 times / day multiple, oral
Recommended
Dose: 40 mg, 3 times / day
Route: oral
Route: multiple
Dose: 40 mg, 3 times / day
Sources:
unhealthy
Other AEs: Hypotension, Tachycardia...
AEs

AEs

AESignificanceDosePopulation
Hypotension
40 mg 3 times / day multiple, oral
Recommended
Dose: 40 mg, 3 times / day
Route: oral
Route: multiple
Dose: 40 mg, 3 times / day
Sources:
unhealthy
Tachycardia
40 mg 3 times / day multiple, oral
Recommended
Dose: 40 mg, 3 times / day
Route: oral
Route: multiple
Dose: 40 mg, 3 times / day
Sources:
unhealthy
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no [IC50 >100 uM]
yes [Activation 28.1838 uM]
yes [IC50 2.72 uM]
yes [IC50 4.9 uM]
yes [IC50 6.13 uM]
yes
yes
yes
yes
yes
yes
yes
PubMed

PubMed

TitleDatePubMed
Evidence for antagonistic activity of endothelin for clonidine induced hypotension and bradycardia.
1992
Characterization of alpha1-adrenoceptor subtypes mediating noradrenaline-induced contraction of rat epididymal vas deferens in calcium-free medium.
1999
[Prevention and release of epidural-morphine-induced urinary retention with phenoxybenzamine and neostigmine].
2000 Dec
Sympathetic nervous system exclusion following experimental subarachnoid haemorrhage prevents vasospasm in rabbits.
2000 Jun 16
The effect of sympathetic nervous system exclusion on cerebral vasospasm following subarachnoid hemorrhage in rabbits.
2001
Phenoxybenzamine is more effective and less harmful than papaverine in the prevention of radial artery vasospasm.
2001 Apr
Effects of L-phenylalanine on acetylcholinesterase and Na(+), K(+)-ATPase activities in adult and aged rat brain.
2001 Apr 30
Adrenergic blockade reduces skeletal muscle glycolysis and Na(+), K(+)-ATPase activity during hemorrhage.
2001 Aug
Brief pretreatment of radial artery conduits with phenoxybenzamine prevents vasoconstriction long term.
2001 Dec
Potency, affinity constants and receptor reserves for noradrenaline and adrenaline on aortae from aged normo- and hypertensive rats.
2001 Feb
Doxazosin inhibits monocyte chemotactic protein 1-directed migration of human monocytes.
2001 May
Responsiveness, affinity constants and receptor reserves for serotonin on aortae of aged normotensive and hypertensive rats.
2001 Oct
Rapid preparation of a patient with pheochromocytoma with labetolol and magnesium sulfate.
2001 Oct
The neurophysiology of myofascial pain syndrome.
2001 Oct
Amplifying effect of the selective calmodulin antagonist, calmidazolium, on the potency of nifedipine to inhibit alpha 1D-adrenoceptor-mediated contraction in the rat aorta.
2002
Modulation of ET(B) receptor-induced arginine-vasopressin secretion by N-methyl-D-aspartate (NMDA) and gamma-aminobutyric acid (GABA)-dependent mechanisms in hypothalamo-neurohypophysial explants.
2002 Aug
Efficacy and safety of doxazosin for perioperative management of patients with pheochromocytoma.
2002 Aug
Suppressive effect of vagal afferents on cervical dorsal horn neurons responding to tooth pulp electrical stimulation in the rat.
2002 Aug
Images in cardiology: Preoperative treatment with phenoxybenzamine restores ECG to normal in a woman with pheochromocytoma.
2002 Aug
Cerebrovascular effects of intravenous dopamine infusions in fetal sheep.
2002 Feb
[Results of surgical treatment of pheochromocytoma at the Institute of Endocrinology of the Clinical Center of Serbia in Belgrade].
2002 Jul
Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3.
2002 Jul
[Current role of intracavernous therapy in the treatment of erectile dysfunction].
2002 Jun
A modern rationale for the use of phenoxybenzamine in urinary tract disorders and other conditions.
2002 Jun
The action of orexin A on passive avoidance learning. Involvement of transmitters.
2002 Mar 15
[Pheochromocytoma of the organ of Zuckerkandl. Apropos of a case].
2002 May
Structure--activity relationships among novel phenoxybenzamine-related beta-chloroethylamines.
2002 May
Atrial supersensitivity to noradrenaline in stressed female rats.
2002 Nov 8
The role of alpha1D-adrenoceptors in prostatic contraction examined using protection studies.
2002 Oct-Dec
Pheochromocytoma: an approach to antihypertensive management.
2002 Sep
Improved survival of patients undergoing palliation of hypoplastic left heart syndrome: lessons learned from 115 consecutive patients.
2002 Sep 24
Characterization of adrenoceptor involvement in skeletal and cardiac myotoxicity Induced by sympathomimetic agents: toward a new bioassay for beta-blockers.
2003 Apr
One hundred years of adrenaline.
2003 Aug
Phaeochromocytoma--views on current management.
2003 Aug
Transmitter characteristics of cutaneous, renal and skeletal muscle small arteries in the rat.
2003 Feb
The vasodilatory effects of hydralazine, nicardipine, nitroglycerin, and fenoldopam in the human umbilical artery.
2003 Feb
Contractile actions of imidazoline alpha-adrenoceptor agonists and effects of noncompetitive alpha1-adrenoceptor antagonists in human vas deferens.
2003 Feb 21
Urethral pressure profile and hemodynamic effects of phenoxybenzamine and prazosin in non-sedated male beagle dogs.
2003 Jan
Serotonin 5-hydroxytryptamine 2A receptor-coupled phospholipase C and phospholipase A2 signaling pathways have different receptor reserves.
2003 Jan
Elevation of the nasal mucosal surface temperature after warming of the feet occurs via a neural reflex.
2003 Jun
Functional characterization of alpha-adrenoceptors mediating pupillary dilation in rats.
2003 Jun 20
Modification of noradrenaline release in pithed spontaneously hypertensive rats by I1-binding sites in addition to alpha2-adrenoceptors.
2003 Mar
Use of a 'hospital-at-home' service for patient optimization before resection of phaeochromocytoma.
2003 Mar
Mechanisms involved in the pressor response to noradrenaline injection into the cingulate cortex of unanesthetized rats.
2003 May
Involvement of transmitters in pituitary adenylate cyclase-activating polypeptide-induced hyperthermia.
2003 Oct 15
Involvement of different receptors in pituitary adenylate cyclase activating polypeptide induced open field activity in rats.
2004 Feb
Patents

Sample Use Guides

Initially, 10 mg twice a day. Dosage should be increased every other day, usually to 20 to 40 mg 2 or 3 times a day, until an optimal dosage is obtained, as judged by blood pressure control.
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment: Phenoxybenzamine hydrochloride (PHEN) exhibited a significant inhibitory effect on the proliferation of both U251 and U87MG glioma cell lines in a positive dose-dependent manner. PHEN apparently attenuated the malignancy of glioma in terms of migration and invasion and also suppressed the tumorigenic capacity both in vitro and in vivo. Mechanism study showed that PHEN promoted tumor suppression by inhibiting the TrkB-Akt pathway. The results of the present study demonstrated that PHEN suppressed the proliferation, migration, invasion, and tumorigenesis of glioma cells, induced LINGO-1 expression, and inhibited the TrkB-Akt pathway, which may prove to be the mechanisms underlying the anti-tumor effect of PHEN on glioma cells.
Unknown
Substance Class Chemical
Created
by admin
on Wed Apr 02 08:33:18 GMT 2025
Edited
by admin
on Wed Apr 02 08:33:18 GMT 2025
Record UNII
0TTZ664R7Z
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DIBENZYLINE
Preferred Name English
PHENOXYBENZAMINE
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
phenoxybenzamine [INN]
Common Name English
BENSYLYT
Common Name English
BENZYLYT
Common Name English
(±)-PHENOXYBENZAMINE
Common Name English
DIBENYLIN
Common Name English
N-(2-CHLOROETHYL)-N-(1-METHYL-2-PHENOXYETHYL)BENZENEMETHANAMINE
Systematic Name English
BENZENEMETHANAMINE, N-(2-CHLOROETHYL)-N-(1-METHYL-2-PHENOXYETHYL)-
Systematic Name English
Phenoxybenzamine [WHO-DD]
Common Name English
PHENOXYBENZAMINE [HSDB]
Common Name English
BENZYLAMINE, N-(2-CHLOROETHYL)-N-(1-METHYL-2-PHENOXYETHYL)-
Systematic Name English
DIBENYLINE
Common Name English
PHENOXYBENZAMINE [VANDF]
Common Name English
N-(2-CHLOROETHYL)-N-(1-METHYL-2-PHENOXYETHYL)BENZYLAMINE
Systematic Name English
PHENOXYBENZAMINE [MI]
Common Name English
N-PHENOXYISOPROPYL-N-BENZYL-.BETA.-CHLOROETHYLAMINE
Systematic Name English
688A
Common Name English
Classification Tree Code System Code
NDF-RT N0000000099
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
WHO-ATC C04AX02
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
NDF-RT N0000175553
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
WHO-VATC QC04AX02
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
NCI_THESAURUS C29713
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
NCI_THESAURUS C45178
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
Code System Code Type Description
RXCUI
8149
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
PRIMARY RxNorm
INN
608
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
PRIMARY
PUBCHEM
4768
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
PRIMARY
CAS
102737-84-8
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
SUPERSEDED
MESH
D010643
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
PRIMARY
HSDB
4005
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
PRIMARY
ChEMBL
CHEMBL753
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
PRIMARY
ECHA (EC/EINECS)
200-446-8
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
PRIMARY
EVMPD
SUB09778MIG
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
PRIMARY
WIKIPEDIA
PHENOXYBENZAMINE
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
PRIMARY
DRUG BANK
DB00925
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
PRIMARY
MERCK INDEX
m8638
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
PRIMARY Merck Index
DRUG CENTRAL
2136
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
PRIMARY
SMS_ID
100000082260
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
PRIMARY
IUPHAR
7268
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
PRIMARY
NCI_THESAURUS
C62065
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
PRIMARY
CAS
59-96-1
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
PRIMARY
EPA CompTox
DTXSID0023458
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
PRIMARY
DAILYMED
0TTZ664R7Z
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
PRIMARY
FDA UNII
0TTZ664R7Z
Created by admin on Wed Apr 02 08:33:18 GMT 2025 , Edited by admin on Wed Apr 02 08:33:18 GMT 2025
PRIMARY
Related Record Type Details
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
SALT/SOLVATE -> PARENT
TRANSPORTER -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC