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

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
[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
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
Sympathetic control of nasal blood flow in the rat mediated by alpha(1)-adrenoceptors.
2001 Feb 16
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
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
Agmatine, an endogenous ligand at imidazoline binding sites, does not antagonize the clonidine-mediated blood pressure reaction.
2002 Feb
Cerebrovascular effects of intravenous dopamine infusions in fetal sheep.
2002 Feb
Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3.
2002 Jul
The action of orexin A on passive avoidance learning. Involvement of transmitters.
2002 Mar 15
Phenoxybenzamine treatment is insufficient to prevent spasm in the radial artery: the effect of other vasodilators.
2003 Aug
Phaeochromocytoma--views on current management.
2003 Aug
Contractile actions of imidazoline alpha-adrenoceptor agonists and effects of noncompetitive alpha1-adrenoceptor antagonists in human vas deferens.
2003 Feb 21
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
Dual effect of agmatine in the bisected rat vas deferens.
2003 Mar
Modification of noradrenaline release in pithed spontaneously hypertensive rats by I1-binding sites in addition to alpha2-adrenoceptors.
2003 Mar
Intrinsic regulation of CGRP release by dental pulp sympathetic fibers.
2003 May
Remifentanil in the management of laparoscopic resection of phaeochromocytoma--case reports.
2003 Nov
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
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