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
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 | ( + / - ) |
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 |
|
[Comparison of selective alpha-1 blockades for alpha-receptors in human hypertrophied prostatic adenomas]. | 1992 Mar |
|
Characterization of alpha1-adrenoceptor subtypes mediating noradrenaline-induced contraction of rat epididymal vas deferens in calcium-free medium. | 1999 |
|
Neurotransmitter-mediated open-field behavioral action of CGRP. | 1999 |
|
[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 |
|
Clinical management of malignant adrenal tumors. | 2001 |
|
Sympathetic control of nasal blood flow in the rat mediated by alpha(1)-adrenoceptors. | 2001 Feb 16 |
|
Inhibition of purified pig and human liver retinyl ester hydrolase by pharmacologic agents. | 2001 May |
|
Doxazosin inhibits monocyte chemotactic protein 1-directed migration of human monocytes. | 2001 May |
|
Responsiveness, affinity constants and receptor reserves for serotonin on aortae of aged normotensive and hypertensive rats. | 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 |
|
Vasopressin reversal of phenoxybenzamine-induced hypotension after the Norwood procedure. | 2002 May |
|
Analgesia in phasic and tonic pain tests in a pharmacological model of autotomy. | 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 |
|
[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 |
|
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 |
|
Transmitter characteristics of cutaneous, renal and skeletal muscle small arteries in the rat. | 2003 Feb |
|
Contractile actions of imidazoline alpha-adrenoceptor agonists and effects of noncompetitive alpha1-adrenoceptor antagonists in human vas deferens. | 2003 Feb 21 |
|
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 |
|
Pheochromocytoma unmasked by imipramine in an 8-year-old girl. | 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 |
|
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 |
|
Mechanisms involved in the pressor response to noradrenaline injection into the cingulate cortex of unanesthetized rats. | 2003 May |
|
Remifentanil in the management of laparoscopic resection of phaeochromocytoma--case reports. | 2003 Nov |
|
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 |
|
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 |
|
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
Substance Class |
Chemical
Created
by
admin
on
Edited
Sun Dec 18 19:24:39 UTC 2022
by
admin
on
Sun Dec 18 19:24:39 UTC 2022
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Record UNII |
0TTZ664R7Z
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Record Status |
Validated (UNII)
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Record Version |
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NDF-RT |
N0000000099
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WHO-ATC |
C04AX02
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NDF-RT |
N0000175553
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WHO-VATC |
QC04AX02
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NCI_THESAURUS |
C29713
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NCI_THESAURUS |
C45178
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8149
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608
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102737-84-8
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D010643
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200-446-8
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SUB09778MIG
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PHENOXYBENZAMINE
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DB00925
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M8638
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2136
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C62065
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59-96-1
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DTXSID0023458
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0TTZ664R7Z
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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