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
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 |
---|---|---|
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
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.
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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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1526007
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m8638
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X1IEG24OHL
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C44435
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ACTIVE MOIETY
SUBSTANCE RECORD