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

Details

Stereochemistry RACEMIC
Molecular Formula C18H22ClNO.ClH
Molecular Weight 340.287
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PHENOXYBENZAMINE HYDROCHLORIDE

SMILES

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

InChI

InChIKey=VBCPVIWPDJVHAN-UHFFFAOYSA-N
InChI=1S/C18H22ClNO.ClH/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;1H

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 (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
Neurotransmitter-mediated open-field behavioral action of CGRP.
1999
Clinical management of malignant adrenal tumors.
2001
Evidence for a non-adrenoceptor, imidazoline-mediated contractile response to oxymetazoline in the porcine isolated rectal artery.
2001 Apr
Effects of L-phenylalanine on acetylcholinesterase and Na(+), K(+)-ATPase activities in adult and aged rat brain.
2001 Apr 30
Vasodilator pre-treatment of human radial arteries; comparison of effects of phenoxybenzamine vs papaverine on norepinephrine-induced contraction in vitro.
2001 Dec
Sympathetic control of nasal blood flow in the rat mediated by alpha(1)-adrenoceptors.
2001 Feb 16
Changes in blood glucose and plasma insulin levels induced by bradykinin in anaesthetized rats.
2001 Nov
The neurophysiology of myofascial pain syndrome.
2001 Oct
Dextran sodium sulphate-induced colitis perturbs muscarinic cholinergic control of colonic epithelial ion transport.
2002 Apr
Suppressive effect of vagal afferents on cervical dorsal horn neurons responding to tooth pulp electrical stimulation in the rat.
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
Atrial supersensitivity to noradrenaline in stressed female rats.
2002 Nov 8
Characterization of adrenoceptor involvement in skeletal and cardiac myotoxicity Induced by sympathomimetic agents: toward a new bioassay for beta-blockers.
2003 Apr
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
Serotonin 5-hydroxytryptamine 2A receptor-coupled phospholipase C and phospholipase A2 signaling pathways have different receptor reserves.
2003 Jan
Studies of alpha-adrenoceptor antagonists on sympathetic mydriasis in rabbits.
2003 Jun
Dual effect of agmatine in the bisected rat vas deferens.
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
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
PHENOXYBENZAMINE HYDROCHLORIDE
MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD  
Common Name English
N-2-PHENOXYISOPROPYL-N-BENZYL-.BETA.-CHLOROETHYLAMINE HYDROCHLORIDE
Common Name English
NSC-37448
Code English
PHENOXYBENZAMINE HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
PHENOXYBENZAMINE HCL
Common Name English
Phenoxybenzamine hydrochloride [WHO-DD]
Common Name English
BENZENEMETHANAMINE, N-(2-CHLOROETHYL)-N-(1-METHYL-2-PHENOXYETHYL)-, HYDROCHLORIDE
Systematic Name English
2-(N-BENZYL-2-CHLOROETHYLAMINO)-1-PHENOXYPROPANE HYDROCHLORIDE
Systematic Name English
PHENOXYBENZAMINE HYDROCHLORIDE [MART.]
Common Name English
PHENOXYBENZAMINE CHLORIDE
Common Name English
BENZENEMETHANAMINE, N-(2-CHLOROETHYL)-N-(1-METHYL-2-PHENOXYETHYL)-, HYDROCHLORIDE (1:1)
Systematic Name English
PHENOXYBENZAMINE HYDROCHLORIDE [MI]
Common Name English
DIBENZYLINE CHLORIDE
Common Name English
PHENOXYBENZAMINE HYDROCHLORIDE [IARC]
Common Name English
PHENOXYBENZAMINE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
PHENOXYBENZAMINE HYDROCHLORIDE [VANDF]
Common Name English
PHENOXYBENZAMINE HYDROCHLORIDE [USP-RS]
Common Name English
BENZYLAMINE, N-(2-CHLOROETHYL)-N-(1-METHYL-2-PHENOXYETHYL)-, HYDROCHLORIDE
Systematic Name English
DIBENZYRAN
Common Name English
DIBENZYLINE HYDROCHLORIDE
Common Name English
DIBENZYLIN
Common Name English
N-(2-Chloroethyl)-N-(1-methyl-2-phenoxyethyl)benzylamine hydrochloride
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C29713
Created by admin on Fri Dec 15 15:07:45 GMT 2023 , Edited by admin on Fri Dec 15 15:07:45 GMT 2023
IARC Phenoxybenzamine hydrochloride
NCI_THESAURUS C45178
Created by admin on Fri Dec 15 15:07:45 GMT 2023 , Edited by admin on Fri Dec 15 15:07:45 GMT 2023
Code System Code Type Description
CAS
34238-85-2
Created by admin on Fri Dec 15 15:07:45 GMT 2023 , Edited by admin on Fri Dec 15 15:07:45 GMT 2023
SUPERSEDED
ECHA (EC/EINECS)
200-569-7
Created by admin on Fri Dec 15 15:07:45 GMT 2023 , Edited by admin on Fri Dec 15 15:07:45 GMT 2023
PRIMARY
EVMPD
SUB03761MIG
Created by admin on Fri Dec 15 15:07:45 GMT 2023 , Edited by admin on Fri Dec 15 15:07:45 GMT 2023
PRIMARY
PUBCHEM
6141
Created by admin on Fri Dec 15 15:07:45 GMT 2023 , Edited by admin on Fri Dec 15 15:07:45 GMT 2023
PRIMARY
RXCUI
71512
Created by admin on Fri Dec 15 15:07:45 GMT 2023 , Edited by admin on Fri Dec 15 15:07:45 GMT 2023
PRIMARY RxNorm
RS_ITEM_NUM
1526007
Created by admin on Fri Dec 15 15:07:45 GMT 2023 , Edited by admin on Fri Dec 15 15:07:45 GMT 2023
PRIMARY
DRUG BANK
DBSALT000480
Created by admin on Fri Dec 15 15:07:45 GMT 2023 , Edited by admin on Fri Dec 15 15:07:45 GMT 2023
PRIMARY
ChEMBL
CHEMBL753
Created by admin on Fri Dec 15 15:07:45 GMT 2023 , Edited by admin on Fri Dec 15 15:07:45 GMT 2023
PRIMARY
NSC
37448
Created by admin on Fri Dec 15 15:07:45 GMT 2023 , Edited by admin on Fri Dec 15 15:07:45 GMT 2023
PRIMARY
EPA CompTox
DTXSID0021127
Created by admin on Fri Dec 15 15:07:45 GMT 2023 , Edited by admin on Fri Dec 15 15:07:45 GMT 2023
PRIMARY
CAS
63-92-3
Created by admin on Fri Dec 15 15:07:45 GMT 2023 , Edited by admin on Fri Dec 15 15:07:45 GMT 2023
PRIMARY
SMS_ID
100000085275
Created by admin on Fri Dec 15 15:07:45 GMT 2023 , Edited by admin on Fri Dec 15 15:07:45 GMT 2023
PRIMARY
MERCK INDEX
m8638
Created by admin on Fri Dec 15 15:07:45 GMT 2023 , Edited by admin on Fri Dec 15 15:07:45 GMT 2023
PRIMARY Merck Index
FDA UNII
X1IEG24OHL
Created by admin on Fri Dec 15 15:07:45 GMT 2023 , Edited by admin on Fri Dec 15 15:07:45 GMT 2023
PRIMARY
NCI_THESAURUS
C44435
Created by admin on Fri Dec 15 15:07:45 GMT 2023 , Edited by admin on Fri Dec 15 15:07:45 GMT 2023
PRIMARY
DAILYMED
X1IEG24OHL
Created by admin on Fri Dec 15 15:07:45 GMT 2023 , Edited by admin on Fri Dec 15 15:07:45 GMT 2023
PRIMARY