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 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 Recommended Dose: 40 mg, 3 times / day Route: oral Route: multiple Dose: 40 mg, 3 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Other AEs: Hypotension, Tachycardia... Other AEs: Hypotension Sources: Tachycardia |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Hypotension | 40 mg 3 times / day multiple, oral Recommended Dose: 40 mg, 3 times / day Route: oral Route: multiple Dose: 40 mg, 3 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
|
Tachycardia | 40 mg 3 times / day multiple, oral Recommended Dose: 40 mg, 3 times / day Route: oral Route: multiple Dose: 40 mg, 3 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
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 |
---|---|---|
Evidence for antagonistic activity of endothelin for clonidine induced hypotension and bradycardia. | 1992 |
|
Characterization of alpha1-adrenoceptor subtypes mediating noradrenaline-induced contraction of rat epididymal vas deferens in calcium-free medium. | 1999 |
|
[Prevention and release of epidural-morphine-induced urinary retention with phenoxybenzamine and neostigmine]. | 2000 Dec |
|
Sympathetic nervous system exclusion following experimental subarachnoid haemorrhage prevents vasospasm in rabbits. | 2000 Jun 16 |
|
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 |
|
Effects of L-phenylalanine on acetylcholinesterase and Na(+), K(+)-ATPase activities in adult and aged rat brain. | 2001 Apr 30 |
|
Adrenergic blockade reduces skeletal muscle glycolysis and Na(+), K(+)-ATPase activity during hemorrhage. | 2001 Aug |
|
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 |
|
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 |
|
Rapid preparation of a patient with pheochromocytoma with labetolol and magnesium sulfate. | 2001 Oct |
|
The neurophysiology of myofascial pain syndrome. | 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 |
|
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 |
|
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 |
|
Cerebrovascular effects of intravenous dopamine infusions in fetal sheep. | 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 |
|
[Current role of intracavernous therapy in the treatment of erectile dysfunction]. | 2002 Jun |
|
A modern rationale for the use of phenoxybenzamine in urinary tract disorders and other conditions. | 2002 Jun |
|
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 |
|
Structure--activity relationships among novel phenoxybenzamine-related beta-chloroethylamines. | 2002 May |
|
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 |
|
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 |
|
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 |
|
Phaeochromocytoma--views on current management. | 2003 Aug |
|
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 |
|
Contractile actions of imidazoline alpha-adrenoceptor agonists and effects of noncompetitive alpha1-adrenoceptor antagonists in human vas deferens. | 2003 Feb 21 |
|
Urethral pressure profile and hemodynamic effects of phenoxybenzamine and prazosin in non-sedated male beagle dogs. | 2003 Jan |
|
Serotonin 5-hydroxytryptamine 2A receptor-coupled phospholipase C and phospholipase A2 signaling pathways have different receptor reserves. | 2003 Jan |
|
Elevation of the nasal mucosal surface temperature after warming of the feet occurs via a neural reflex. | 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 |
|
Involvement of transmitters in pituitary adenylate cyclase-activating polypeptide-induced hyperthermia. | 2003 Oct 15 |
|
Involvement of different receptors in pituitary adenylate cyclase activating polypeptide induced open field activity in rats. | 2004 Feb |
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
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Record UNII |
0TTZ664R7Z
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C04AX02
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C29713
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C45178
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Related Record | Type | Details | ||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR | |||
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SALT/SOLVATE -> PARENT | |||
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TRANSPORTER -> INHIBITOR |
Related Record | Type | Details | ||
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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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