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 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 |
|---|---|---|
| [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 |
|
| 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 |
|
| Sympathetic control of nasal blood flow in the rat mediated by alpha(1)-adrenoceptors. | 2001 Feb 16 |
|
| 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 |
|
| 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 |
|
| Agmatine, an endogenous ligand at imidazoline binding sites, does not antagonize the clonidine-mediated blood pressure reaction. | 2002 Feb |
|
| Cerebrovascular effects of intravenous dopamine infusions in fetal sheep. | 2002 Feb |
|
| Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3. | 2002 Jul |
|
| The action of orexin A on passive avoidance learning. Involvement of transmitters. | 2002 Mar 15 |
|
| 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 |
|
| Contractile actions of imidazoline alpha-adrenoceptor agonists and effects of noncompetitive alpha1-adrenoceptor antagonists in human vas deferens. | 2003 Feb 21 |
|
| 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 |
|
| 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 |
|
| Intrinsic regulation of CGRP release by dental pulp sympathetic fibers. | 2003 May |
|
| Remifentanil in the management of laparoscopic resection of phaeochromocytoma--case reports. | 2003 Nov |
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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| Classification Tree | Code System | Code | ||
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NDF-RT |
N0000000099
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C04AX02
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QC04AX02
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C29713
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C45178
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)