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
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
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 |
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 Date1953 |
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 |
---|---|---|
THE EFFECT OF L-3, 4-DIHYDROXYPHENYLALANINE AND DL-5-HYDROXYTRYPTOPHAN ON RIGIDITY AND TREMOR INDUCED BY RESERPINE, CHLORPROMAZINE AND PHENOXYBENZAMINE. | 1964 Apr |
|
Paradoxical rise in blood pressure during propranolol treatment. | 1975 Dec 13 |
|
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 |
|
Problems with the management of a case of phaeochromocytoma: case report. | 2001 Dec |
|
Laparoscopic partial adrenalectomy for recurrent pheochromocytoma after open partial adrenalectomy in von Hippel-Lindau disease. | 2002 Apr |
|
Dextran sodium sulphate-induced colitis perturbs muscarinic cholinergic control of colonic epithelial ion transport. | 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 |
|
Efficacy and safety of doxazosin for perioperative management of patients with pheochromocytoma. | 2002 Aug |
|
Endoscopic treatment of solitary, bilateral, multiple, and recurrent pheochromocytomas and paragangliomas. | 2002 Aug |
|
Endogenous norepinephrine regulates blood flow to the intact rat tibia. | 2002 Mar |
|
Vasopressin reversal of phenoxybenzamine-induced hypotension after the Norwood procedure. | 2002 May |
|
Effects of noradrenaline on cytosolic concentrations of Ca(2+) in cultured corpus cavernosum smooth muscle cells of the rabbit. | 2002 May 17 |
|
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 |
|
Pheochromocytoma: an approach to antihypertensive management. | 2002 Sep |
|
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 |
|
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 |
|
Phaeochromocytoma--views on current management. | 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 |
|
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 |
|
Elevation of the nasal mucosal surface temperature after warming of the feet occurs via a neural reflex. | 2003 Jun |
|
Studies of alpha-adrenoceptor antagonists on sympathetic mydriasis in rabbits. | 2003 Jun |
|
Pheochromocytoma unmasked by imipramine in an 8-year-old girl. | 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 |
|
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 |
|
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 |
|
Involvement of transmitters in pituitary adenylate cyclase-activating polypeptide-induced hyperthermia. | 2003 Oct 15 |
|
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 |
|
Increased reactivity of murine mesenteric veins to adrenergic agonists: functional evidence supporting increased alpha1-adrenoceptor reserve in veins compared with arteries. | 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
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
Fri Dec 15 15:07:45 GMT 2023
by
admin
on
Fri Dec 15 15:07:45 GMT 2023
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Record UNII |
X1IEG24OHL
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Record Status |
Validated (UNII)
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Record Version |
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NCI_THESAURUS |
C29713
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IARC | Phenoxybenzamine hydrochloride | ||
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NCI_THESAURUS |
C45178
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