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

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 ( + / - )

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
THE EFFECT OF L-3, 4-DIHYDROXYPHENYLALANINE AND DL-5-HYDROXYTRYPTOPHAN ON RIGIDITY AND TREMOR INDUCED BY RESERPINE, CHLORPROMAZINE AND PHENOXYBENZAMINE.
1964 Apr
Evidence for antagonistic activity of endothelin for clonidine induced hypotension and bradycardia.
1992
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
Evidence for a non-adrenoceptor, imidazoline-mediated contractile response to oxymetazoline in the porcine isolated rectal artery.
2001 Apr
Adrenergic blockade reduces skeletal muscle glycolysis and Na(+), K(+)-ATPase activity during hemorrhage.
2001 Aug
Phenoxybenzamine binding reveals the helical orientation of the third transmembrane domain of adrenergic receptors.
2001 Aug 17
Vasodilator pre-treatment of human radial arteries; comparison of effects of phenoxybenzamine vs papaverine on norepinephrine-induced contraction in vitro.
2001 Dec
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
Doxazosin inhibits monocyte chemotactic protein 1-directed migration of human monocytes.
2001 May
Rapid preparation of a patient with pheochromocytoma with labetolol and magnesium sulfate.
2001 Oct
Evaluation of functional response of cerebral arteries by a new morphometric technique.
2001 Oct 8
Laparoscopic partial adrenalectomy for recurrent pheochromocytoma after open partial adrenalectomy in von Hippel-Lindau disease.
2002 Apr
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
Endoscopic treatment of solitary, bilateral, multiple, and recurrent pheochromocytomas and paragangliomas.
2002 Aug
A placebo-controlled double-blind study of the effect of phenoxybenzamine in benign prostatic obstruction. 1978.
2002 Feb
Agmatine, an endogenous ligand at imidazoline binding sites, does not antagonize the clonidine-mediated blood pressure reaction.
2002 Feb
alpha(1A)-adrenoceptors mediate sympathetically evoked pupillary dilation in rats.
2002 Feb
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
Adrenergic mechanisms in antinociceptive effects of non steroidal anti-inflammatory drugs in acute thermal nociception in mice.
2002 May
Pheochromocytoma: an approach to antihypertensive management.
2002 Sep
Norepinephrine release is reduced by I(1)-receptors in addition to alpha(2)-adrenoceptors.
2003 Dec
Comparative efficacies and durations of action of phenoxybenzamine, verapamil/nitroglycerin solution, and papaverine as topical antispasmodics for radial artery coronary bypass grafting.
2003 Dec
The vasodilatory effects of hydralazine, nicardipine, nitroglycerin, and fenoldopam in the human umbilical artery.
2003 Feb
Functional characterisation of alpha(1)-adrenoceptors in denervated rat vas deferens.
2003 Jul
Studies of alpha-adrenoceptor antagonists on sympathetic mydriasis in rabbits.
2003 Jun
Biochemical diagnosis of pheochromocytoma: how to distinguish true- from false-positive test results.
2003 Jun
Expression of glycerokinase in brown adipose tissue is stimulated by the sympathetic nervous system.
2003 Jun
Functional characterization of alpha-adrenoceptors mediating pupillary dilation in rats.
2003 Jun 20
Dual effect of agmatine in the bisected rat vas deferens.
2003 Mar
Use of a 'hospital-at-home' service for patient optimization before resection of phaeochromocytoma.
2003 Mar
Remifentanil in the management of laparoscopic resection of phaeochromocytoma--case reports.
2003 Nov
Role of alpha-adrenergic receptors in the effect of the beta-adrenergic receptor ligands, CGP 12177, bupranolol, and SR 59230A, on the contraction of rat intrapulmonary artery.
2004 Apr
Involvement of different receptors in pituitary adenylate cyclase activating polypeptide induced open field activity in rats.
2004 Feb
Pheochromocytoma and pregnancy: a case report and review of anesthetic management.
2004 Feb
Release and functional role of neuropeptide Y as a sympathetic modulator in human saphenous vein biopsies.
2004 Jan
Effect of moderate pressure distention on the human saphenous vein vasomotor function.
2004 Jan
Medicinal plants in Suriname: hypotensive effect of Gossypium barbadense.
2004 Mar
Alteration of the critical arteriovenous oxygen saturation relationship by sustained afterload reduction after the Norwood procedure.
2004 Mar
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 Fri Dec 15 15:07:45 GMT 2023
Edited
by admin
on Fri Dec 15 15:07:45 GMT 2023
Record UNII
X1IEG24OHL
Record Status Validated (UNII)
Record Version
  • Download
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
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
IMPURITY -> PARENT
IMPURITY -> PARENT
IMPURITY -> PARENT
Related Record Type Details
ACTIVE MOIETY