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
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
DescriptionCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/11395517
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.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2095203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11395517 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Palliative | DIBENZYLINE Approved UseINDICATION 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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse 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 Sources: Page: p.2Tachycardia |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical 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
Title | Date | PubMed |
---|---|---|
Paradoxical rise in blood pressure during propranolol treatment. | 1975 Dec 13 |
|
[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 |
|
[Comparison of selective alpha-1 blockades for alpha-receptors in human hypertrophied prostatic adenomas]. | 1992 Mar |
|
[Prevention and release of epidural-morphine-induced urinary retention with phenoxybenzamine and neostigmine]. | 2000 Dec |
|
The effect of sympathetic nervous system exclusion on cerebral vasospasm following subarachnoid hemorrhage in rabbits. | 2001 |
|
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 |
|
Rapid preparation of a patient with pheochromocytoma with labetolol and magnesium sulfate. | 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 |
|
Laparoscopic partial adrenalectomy for recurrent pheochromocytoma after open partial adrenalectomy in von Hippel-Lindau disease. | 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 |
|
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 |
|
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 |
|
[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 |
|
Alpha blockade in preoperative preparation of patients with pheochromocytomas. | 2002 Jul-Sep |
|
Endogenous norepinephrine regulates blood flow to the intact rat tibia. | 2002 Mar |
|
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 |
|
Adrenergic mechanisms in antinociceptive effects of non steroidal anti-inflammatory drugs in acute thermal nociception in mice. | 2002 May |
|
Vasopressin reversal of phenoxybenzamine-induced hypotension after the Norwood procedure. | 2002 May |
|
Structure--activity relationships among novel phenoxybenzamine-related beta-chloroethylamines. | 2002 May |
|
Motilin regulates interdigestive gastric blood flow in dogs. | 2002 Nov |
|
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 |
|
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 |
|
One hundred years of adrenaline. | 2003 Aug |
|
Phenoxybenzamine treatment is insufficient to prevent spasm in the radial artery: the effect of other vasodilators. | 2003 Aug |
|
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 |
|
Urethral pressure profile and hemodynamic effects of phenoxybenzamine and prazosin in non-sedated male beagle dogs. | 2003 Jan |
|
Studies of alpha-adrenoceptor antagonists on sympathetic mydriasis in rabbits. | 2003 Jun |
|
Expression of glycerokinase in brown adipose tissue is stimulated by the sympathetic nervous system. | 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 |
|
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 different receptors in pituitary adenylate cyclase activating polypeptide induced open field activity in rats. | 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 |
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26409450
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 | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Systematic Name | English | ||
|
Brand Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
NDF-RT |
N0000000099
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
||
|
WHO-ATC |
C04AX02
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
||
|
NDF-RT |
N0000175553
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
||
|
WHO-VATC |
QC04AX02
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
||
|
NCI_THESAURUS |
C29713
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
||
|
NCI_THESAURUS |
C45178
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
8149
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
PRIMARY | RxNorm | ||
|
608
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
PRIMARY | |||
|
4768
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
PRIMARY | |||
|
102737-84-8
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
SUPERSEDED | |||
|
D010643
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
PRIMARY | |||
|
4005
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
PRIMARY | |||
|
CHEMBL753
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
PRIMARY | |||
|
200-446-8
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
PRIMARY | |||
|
SUB09778MIG
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
PRIMARY | |||
|
PHENOXYBENZAMINE
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
PRIMARY | |||
|
DB00925
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
PRIMARY | |||
|
M8638
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
PRIMARY | Merck Index | ||
|
2136
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
PRIMARY | |||
|
7268
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
PRIMARY | |||
|
C62065
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
PRIMARY | |||
|
59-96-1
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
PRIMARY | |||
|
DTXSID0023458
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
PRIMARY | |||
|
0TTZ664R7Z
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
PRIMARY | |||
|
0TTZ664R7Z
Created by
admin on Sun Dec 18 19:24:40 UTC 2022 , Edited by admin on Sun Dec 18 19:24:40 UTC 2022
|
PRIMARY |
ACTIVE MOIETY
SALT/SOLVATE (PARENT)