U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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

-5.34297608E11
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 (max)
Recommended
Dose: 40 mg, 3 times / day
Route: oral
Route: multiple
Dose: 40 mg, 3 times / day
Sources: Page: p.2
unhealthy
Health Status: unhealthy
Condition: Pheochromocytoma
Sources: Page: p.2
Other AEs: Hypotension, Tachycardia...
Other AEs:
Hypotension
Tachycardia
Sources: Page: p.2
AEs

AEs

AESignificanceDosePopulation
Hypotension
40 mg 3 times / day multiple, oral (max)
Recommended
Dose: 40 mg, 3 times / day
Route: oral
Route: multiple
Dose: 40 mg, 3 times / day
Sources: Page: p.2
unhealthy
Health Status: unhealthy
Condition: Pheochromocytoma
Sources: Page: p.2
Tachycardia
40 mg 3 times / day multiple, oral (max)
Recommended
Dose: 40 mg, 3 times / day
Route: oral
Route: multiple
Dose: 40 mg, 3 times / day
Sources: Page: p.2
unhealthy
Health Status: unhealthy
Condition: Pheochromocytoma
Sources: Page: p.2
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
[Effects of 2-(4-benzyl-piperidino)-1-(4-hydroxyphenyl)-1-propanol (ifenprodil) on the cardiovascular system in vivo].
1975 Sep
Evidence for antagonistic activity of endothelin for clonidine induced hypotension and bradycardia.
1992
[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
[Sympathetically maintained pain syndrome--a case report].
2001
The effect of sympathetic nervous system exclusion on cerebral vasospasm following subarachnoid hemorrhage in rabbits.
2001
The effect of sympathetic activity on thermal hyperalgesia in capsaicin-treated skin during body cooling and warming.
2001
Evidence for a non-adrenoceptor, imidazoline-mediated contractile response to oxymetazoline in the porcine isolated rectal artery.
2001 Apr
Vasodilator pre-treatment of human radial arteries; comparison of effects of phenoxybenzamine vs papaverine on norepinephrine-induced contraction in vitro.
2001 Dec
Pheochromocytoma in a pregnant woman with multiple endocrine neoplasia type 2a.
2001 Dec
Brief pretreatment of radial artery conduits with phenoxybenzamine prevents vasoconstriction long term.
2001 Dec
Changes in blood glucose and plasma insulin levels induced by bradykinin in anaesthetized rats.
2001 Nov
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
Laparoscopic partial adrenalectomy for recurrent pheochromocytoma after open partial adrenalectomy in von Hippel-Lindau disease.
2002 Apr
Dextran sodium sulphate-induced colitis perturbs muscarinic cholinergic control of colonic epithelial ion transport.
2002 Apr
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
Images in cardiology: Preoperative treatment with phenoxybenzamine restores ECG to normal in a woman with pheochromocytoma.
2002 Aug
alpha(1A)-adrenoceptors mediate sympathetically evoked pupillary dilation in rats.
2002 Feb
Cerebrovascular effects of intravenous dopamine infusions in fetal sheep.
2002 Feb
Alpha blockade in preoperative preparation of patients with pheochromocytomas.
2002 Jul-Sep
The action of orexin A on passive avoidance learning. Involvement of transmitters.
2002 Mar 15
Vasopressin reversal of phenoxybenzamine-induced hypotension after the Norwood procedure.
2002 May
Structure--activity relationships among novel phenoxybenzamine-related beta-chloroethylamines.
2002 May
Effects of noradrenaline on cytosolic concentrations of Ca(2+) in cultured corpus cavernosum smooth muscle cells of the rabbit.
2002 May 17
Motilin regulates interdigestive gastric blood flow in dogs.
2002 Nov
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
Neurotransmitter release in an arterial preparation and the action of alpha-adrenoceptor antagonists.
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
[Haematemesis and dysphagia in a 20-year-old woman with congenital spine malformation and situs inversus partialis].
2003 Apr
Characterization of adrenoceptor involvement in skeletal and cardiac myotoxicity Induced by sympathomimetic agents: toward a new bioassay for beta-blockers.
2003 Apr
Phaeochromocytoma--views on current management.
2003 Aug
Norepinephrine release is reduced by I(1)-receptors in addition to alpha(2)-adrenoceptors.
2003 Dec
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
Biochemical diagnosis of pheochromocytoma: how to distinguish true- from false-positive test results.
2003 Jun
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
Intrinsic regulation of CGRP release by dental pulp sympathetic fibers.
2003 May
Mechanisms involved in the pressor response to noradrenaline injection into the cingulate cortex of unanesthetized rats.
2003 May
Pretreatment with phenoxybenzamine attenuates the radial artery's vasoconstrictor response to alpha-adrenergic stimuli.
2003 Nov
Photoperiod modulates the effects of norepinephrine on lymphocyte proliferation in Siberian hamsters.
2003 Oct
Involvement of transmitters in pituitary adenylate cyclase-activating polypeptide-induced hyperthermia.
2003 Oct 15
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 Thu Jul 06 22:21:41 UTC 2023
Edited
by admin
on Thu Jul 06 22:21:41 UTC 2023
Record UNII
0TTZ664R7Z
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
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
DIBENZYLINE
Brand 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 Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
WHO-ATC C04AX02
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
NDF-RT N0000175553
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
WHO-VATC QC04AX02
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
NCI_THESAURUS C29713
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
NCI_THESAURUS C45178
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
Code System Code Type Description
RXCUI
8149
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
PRIMARY RxNorm
INN
608
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
PRIMARY
PUBCHEM
4768
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
PRIMARY
CAS
102737-84-8
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
SUPERSEDED
MESH
D010643
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
PRIMARY
HSDB
4005
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
PRIMARY
ChEMBL
CHEMBL753
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
PRIMARY
ECHA (EC/EINECS)
200-446-8
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
PRIMARY
EVMPD
SUB09778MIG
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
PRIMARY
WIKIPEDIA
PHENOXYBENZAMINE
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
PRIMARY
DRUG BANK
DB00925
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
PRIMARY
MERCK INDEX
M8638
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
PRIMARY Merck Index
DRUG CENTRAL
2136
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
PRIMARY
SMS_ID
100000082260
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
PRIMARY
IUPHAR
7268
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
PRIMARY
NCI_THESAURUS
C62065
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
PRIMARY
CAS
59-96-1
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
PRIMARY
EPA CompTox
DTXSID0023458
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
PRIMARY
DAILYMED
0TTZ664R7Z
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
PRIMARY
FDA UNII
0TTZ664R7Z
Created by admin on Thu Jul 06 22:21:42 UTC 2023 , Edited by admin on Thu Jul 06 22:21:42 UTC 2023
PRIMARY
Related Record Type Details
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC