Identification
- Summary
Phentolamine is an alpha-adrenergic blocker used to treat hypertensive episodes, diagnose pheochromocytoma, treat norepinephrine administration site reactions, and reverse soft tissue anesthesia and mydriasis.
- Brand Names
- Oraverse
- Generic Name
- Phentolamine
- DrugBank Accession Number
- DB00692
- Background
Phentolamine is a reversible, non-selective alpha-adrenergic blocker that induces vasodilation. While initially introduced to the market for the treatment of hypertension, this clinical use was halted due to cardiovascular and gastrointestinal adverse effects with the prolonged use of large oral doses of phentolamine.1,4 It has several therapeutic uses, including the treatment of hypertensive episodes, prevention of norepinephrine-induced extravasation, diagnosis of pheochromocytoma, reversal of soft-tissue anesthesia, and treatment of pharmacologically-induced mydriasis.8,7,5 Phentolamine is administered intravenously, intramuscularly, submucosally, and topically.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Phentolamine (DB00692)
- Weight
- Average: 281.3523
Monoisotopic: 281.152812245 - Chemical Formula
- C17H19N3O
- Synonyms
- 2-(N-(m-hydroxyphenyl)-p-toluidinomethyl)imidazoline
- 3-((4,5-DIHYDRO-1H-IMIDAZOL-2-YLMETHYL)(4-METHYLPHENYL)AMINO)PHENOL
- Fentolamina
- Phentolamin
- Phentolamine
- Phentolaminum
- External IDs
- C 7337
- C 7337 Ciba
Pharmacology
- Indication
When used intravenously or intramuscularly, phentolamine is used to prevent or control hypertensive episodes that may occur in a patient with pheochromocytoma due to stress or manipulation during preoperative preparation and surgical excision. It is also used to prevent or treat dermal necrosis and sloughing following intravenous administration or extravasation of norepinephrine. It may be used to diagnose pheochromocytoma by the phentolamine-blocking test.8
Submucosal injection of phentolamine is indicated for the reversal of soft-tissue anesthesia (e.g. anesthesia of the lip and tongue) and the associated functional deficits resulting from an intraoral submucosal injection of a local anesthetic containing a vasoconstrictor in patients three years old and older.7
Phentolamine ophthalmic solution is used to treat pharmacologically-induced mydriasis produced by adrenergic agonists (e.g., phenylephrine) or parasympatholytic (e.g., tropicamide) agents.5
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Reversal of Mydriasis •••••••••••• Reversal of Mydriasis •••••••••••• Prophylaxis of Necrosis caused by norepinephrine extravasation •••••••••••• Diagnostic agent Pheochromocytoma •••••••••••• Reversal of Soft tissue anesthesia (numbness) •••••••••••• - Contraindications & Blackbox Warnings
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Phentolamine produces an alpha-adrenergic block of a relatively short duration.7 Phentolamine induces vasodilatation of vascular smooth muscle and pupils.7,5 When used in an ophthalmic solution, the onset of pupil dilation generally occurred in 30 minutes, with the maximal effect seen in 60 to 90 minutes. Pupil dilation lasted for at least 24 hours.5 Phentolamine also has direct but less marked positive inotropic and chronotropic effects on cardiac muscle and vasodilator effects on vascular smooth muscle;8 however, phentolamine is not believed to affect contractile or adenyl cyclase function.1 Large doses can lead to a mild sympatholytic action.1
Some evidence suggests that phentolamine also stimulates beta-adrenergic receptors, thereby causing peripheral vasodilation.1 Phentolamine was shown to stimulate insulin secretion, possibly related to its blocking actions on ATP-sensitive K+ channels.1,3
- Mechanism of action
Phentolamine is a reversible, competitive antagonist at alpha-1 and alpha-2 adrenergic receptors.2,5 It causes vasodilation of vascular smooth muscles.7 Pupil dilation is primarily controlled by the radial iris dilator muscles surrounding the pupil, which are activated by the alpha-1 adrenergic receptors. Phentolamine reversibly binds to these receptors and reduces pupil diameter. By blocking alpha-1 adrenergic receptors, phentolamine can also be used to reverse mydriasis induced by muscarinic antagonists.5
Target Actions Organism AAlpha-1 adrenergic receptors antagonistHumans UAlpha-2 adrenergic receptors antagonistHumans UATP-sensitive inward rectifier potassium channel 11 blockerHumans - Absorption
The peak concentrations of phentolamine are achieved within 10 to 20 minutes following submucosal administration. The Cmax was higher in children with greater weights.7
Following topical ocular administration of phentolamine ophthalmic solution 0.75%, the peak concentration levels were achieved between 15 minutes and one hour after dosing with the median value of 0.45 ng/mL.5
- Volume of distribution
While there is limited information on phentolamine distribution, the drug is reported to cross the blood-brain barrier.2
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Approximately 13% of a single intravenous dose appears in the urine as unchanged drug.8
- Half-life
Phentolamine has a half-life of 19 minutes following intravenous administration.8 The terminal elimination half-life of phentolamine was approximately two to three hours following submucosal administration.7
- Clearance
Not Available
- Adverse Effects
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The oral LD50 of phentolamine mesylate, a salt of phentolamine, was 1250 mg/kg in rats and 1000-1100 mg/kg in mice.6,8
No deaths due to acute poisoning with phentolamine have been reported. Overdosage with phentolamine is characterized chiefly by cardiovascular disturbances, such as arrhythmias, tachycardia, hypotension, and possibly shock. Other possible signs and symptoms include excitation, headache, sweating, pupillary contraction, visual disturbances, nausea, vomiting, diarrhea, and hypoglycemia. There is no specific antidote: Treatment consists of appropriate monitoring and supportive care. A plasma expander and norepinephrine may be administered to manage decreased blood pressure.7,8
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbaloparatide The risk or severity of adverse effects can be increased when Phentolamine is combined with Abaloparatide. Acebutolol Acebutolol may increase the orthostatic hypotensive activities of Phentolamine. Aceclofenac The therapeutic efficacy of Phentolamine can be decreased when used in combination with Aceclofenac. Acemetacin The therapeutic efficacy of Phentolamine can be decreased when used in combination with Acemetacin. Acetylsalicylic acid Acetylsalicylic acid may decrease the antihypertensive activities of Phentolamine. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Phentolamine mesylate Y7543E5K9T 65-28-1 OGIYDFVHFQEFKQ-UHFFFAOYSA-N - International/Other Brands
- Regitin (Novartis) / Regitina (Novartis) / Vigamed (Grupo Cimed)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Oraverse Solution 0.4 mg / 1.7 mL Submucosal Septodont 2014-09-17 Not applicable Canada 
Oraverse Injection, solution 0.235 mg/1mL Submucosal Septodont, Inc. 2011-06-01 Not applicable US 
OraVerse Injection, solution 0.4 mg/1.7mL Submucosal Novalar Pharmaceuticals 2008-05-23 Not applicable US Phentolamine Mesylate Injection 5 mg/1mL Intramuscular; Intravenous; Parenteral Sandoz Inc 2012-06-01 2013-07-31 US Phentolamine Mesylate Injection Sandoz Standard Solution 5 mg / mL Intramuscular; Intravenous Sandoz Canada Incorporated 2001-06-15 Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Phentolamine Mesylate Injection 5 mg/1 Intramuscular; Intravenous TAGI Pharma, Inc. 2017-07-15 Not applicable US Phentolamine Mesylate Injection 5 mg/1 Intramuscular; Intravenous Precision Dose Inc. 2017-07-15 Not applicable US Phentolamine Mesylate Injection, powder, for solution 5 mg/1mL Intramuscular; Intravenous West-Ward Pharmaceuticals Corp 1998-05-15 Not applicable US Phentolamine Mesylate Injection, powder, for solution 5 mg/1mL Intramuscular; Intravenous Bedford Pharmaceuticals 1998-05-15 2015-09-30 US - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Phentolamine Mesylate Phentolamine mesylate (5 mg/1mL) Injection Intramuscular; Intravenous; Parenteral Sandoz Inc 2012-06-01 2013-07-31 US
Categories
- ATC Codes
- V03AB36 — Phentolamine
- V03AB — Antidotes
- V03A — ALL OTHER THERAPEUTIC PRODUCTS
- V03 — ALL OTHER THERAPEUTIC PRODUCTS
- V — VARIOUS
- Drug Categories
- Adrenergic Agents
- Adrenergic alpha-1 Receptor Antagonists
- Adrenergic alpha-Antagonists
- Adrenergic Antagonists
- Agents that produce hypertension
- Antidotes
- Antihypertensive Agents
- Cardiovascular Agents
- Drugs that are Mainly Renally Excreted
- Hypotensive Agents
- Imidazoles
- Imidazoline Derivatives
- Neurotransmitter Agents
- Non-selective Alfa-adrenergic Blocking Agents
- Peripheral alpha-1 blockers
- Peripheral Vasodilators
- Sympatholytic (Adrenergic Blocking) Agents
- Vasodilating Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as alkyldiarylamines. These are tertiary alkylarylamines having two aryl and one alkyl groups attached to the amino group.
- Kingdom
- Organic compounds
- Super Class
- Organic nitrogen compounds
- Class
- Organonitrogen compounds
- Sub Class
- Amines
- Direct Parent
- Alkyldiarylamines
- Alternative Parents
- m-Aminophenols / Aniline and substituted anilines / Aminotoluenes / 1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids / Imidolactams / Imidazolines / Propargyl-type 1,3-dipolar organic compounds / Carboximidamides / Carboxamidines show 4 more
- Substituents
- 1-hydroxy-2-unsubstituted benzenoid / 1-hydroxy-4-unsubstituted benzenoid / 2-imidazoline / Alkyldiarylamine / Amidine / Aminophenol / Aminotoluene / Aniline or substituted anilines / Aromatic heteromonocyclic compound / Azacycle show 15 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- tertiary amino compound, substituted aniline, imidazoles, phenols (CHEBI:8081)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- Z468598HBV
- CAS number
- 50-60-2
- InChI Key
- MRBDMNSDAVCSSF-UHFFFAOYSA-N
- InChI
- InChI=1S/C17H19N3O/c1-13-5-7-14(8-6-13)20(12-17-18-9-10-19-17)15-3-2-4-16(21)11-15/h2-8,11,21H,9-10,12H2,1H3,(H,18,19)
- IUPAC Name
- 3-{[(4,5-dihydro-1H-imidazol-2-yl)methyl](4-methylphenyl)amino}phenol
- SMILES
- CC1=CC=C(C=C1)N(CC1=NCCN1)C1=CC(O)=CC=C1
References
- General References
- Gould L, Reddy CV: Phentolamine. Am Heart J. 1976 Sep;92(3):397-402. doi: 10.1016/s0002-8703(76)80121-4. [Article]
- Raja SN, Treede RD, Davis KD, Campbell JN: Systemic alpha-adrenergic blockade with phentolamine: a diagnostic test for sympathetically maintained pain. Anesthesiology. 1991 Apr;74(4):691-8. doi: 10.1097/00000542-199104000-00012. [Article]
- Proks P, Ashcroft FM: Phentolamine block of KATP channels is mediated by Kir6.2. Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11716-20. doi: 10.1073/pnas.94.21.11716. [Article]
- Brock G: Oral phentolamine (Vasomax). Drugs Today (Barc). 2000 Feb-Mar;36(2-3):121-4. doi: 10.1358/dot.2000.36.2-3.568785. [Article]
- FDA Approved Drug Products: RYZUMVI (phentolamine ophthalmic solution) 0.75%, for topical ophthalmic use [Link]
- Oraverse: Phentolamine mesylate MSDS [Link]
- DailyMed Label: ORAVERSE (phentolamine mesylate) submucosal injection, solution [Link]
- DailyMed Label: PHENTOLAMINE MESYLATE intravenous or intramuscular injection, powder, for solution [Link]
- External Links
- Human Metabolome Database
- HMDB0014830
- PubChem Compound
- 5775
- PubChem Substance
- 46506535
- ChemSpider
- 5571
- BindingDB
- 31046
- 8153
- ChEBI
- 8081
- ChEMBL
- CHEMBL597
- ZINC
- ZINC000000020251
- Therapeutic Targets Database
- DAP000299
- PharmGKB
- PA450926
- Guide to Pharmacology
- GtP Drug Page
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Phentolamine
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Anesthesia, Reversal / Dental Local Anesthesia / Local Anaesthesia therapy 1 4 Completed Treatment Local Anaesthesia therapy 1 4 Not Yet Recruiting Prevention Pre-eclampsia Aggravated / Pre-Eclampsia; Complicating Pregnancy 1 4 Recruiting Basic Science Vasoconstriction / Vasodilation 1 3 Completed Treatment Dental Local Anesthesia 2
Pharmacoeconomics
- Manufacturers
- Novalar pharmaceuticals inc
- Bedford laboratories div ben venue laboratories inc
- Novartis pharmaceuticals corp
- Sanofi aventis us llc
- Glaxosmithkline
- Perrigo co
- Ranbaxy laboratories ltd
- Mcneil consumer healthcare
- Packagers
- Bedford Labs
- Ben Venue Laboratories Inc.
- Novalar Pharmaceuticals Inc.
- Novartis AG
- Novocol Pharmaceutical Canada
- Dosage Forms
Form Route Strength Injection, solution Submucosal 0.235 mg/1mL Injection, solution Submucosal 0.4 mg/1.7mL Injection, solution Submucosal 400 MICROGRAMMI/1.7ML Solution Submucosal 0.4 mg / 1.7 mL Injection Intramuscular; Intravenous 5 mg/1 Injection Intramuscular; Intravenous; Parenteral 5 mg/1mL Injection, powder, for solution Intramuscular; Intravenous 5 mg/1mL Powder Not applicable 1 g/1g Solution Intramuscular; Intravenous 5 mg / mL Injection, powder, lyophilized, for suspension Intramuscular; Intravenous 5 mg/1mL Solution Intramuscular; Intravenous 10 mg / mL Powder, for solution Intramuscular; Intravenous 5 mg / amp - Prices
Unit description Cost Unit Phentolamine 5 mg vial 84.0USD vial DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6764678 No 2004-07-20 2021-05-11 US US7569230 No 2009-08-04 2023-10-17 US US6872390 No 2005-03-29 2021-05-11 US US7229630 No 2007-06-12 2023-06-20 US US7575757 No 2009-08-18 2025-04-21 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 181 https://www.spectrumchemical.com/media/sds/P1687_AGHS.pdf logP 3.3 Not Available - Predicted Properties
Property Value Source Water Solubility 0.272 mg/mL ALOGPS logP 2.91 ALOGPS logP 2.52 Chemaxon logS -3 ALOGPS pKa (Strongest Acidic) 9.78 Chemaxon pKa (Strongest Basic) 9.02 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 47.86 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 84.25 m3·mol-1 Chemaxon Polarizability 31.37 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9293 Blood Brain Barrier + 0.838 Caco-2 permeable - 0.6104 P-glycoprotein substrate Substrate 0.772 P-glycoprotein inhibitor I Non-inhibitor 0.9329 P-glycoprotein inhibitor II Inhibitor 0.8031 Renal organic cation transporter Inhibitor 0.7497 CYP450 2C9 substrate Non-substrate 0.6892 CYP450 2D6 substrate Non-substrate 0.5668 CYP450 3A4 substrate Non-substrate 0.6313 CYP450 1A2 substrate Non-inhibitor 0.9046 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Inhibitor 0.8931 CYP450 2C19 inhibitor Non-inhibitor 0.8454 CYP450 3A4 inhibitor Non-inhibitor 0.831 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7661 Ames test Non AMES toxic 0.6266 Carcinogenicity Non-carcinogens 0.8555 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.4366 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.6149 hERG inhibition (predictor II) Inhibitor 0.59
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 182.5343984 predictedDarkChem Lite v0.1.0 [M-H]- 182.4186984 predictedDarkChem Lite v0.1.0 [M-H]- 162.72264 predictedDeepCCS 1.0 (2019) [M+H]+ 183.3238984 predictedDarkChem Lite v0.1.0 [M+H]+ 182.7420984 predictedDarkChem Lite v0.1.0 [M+H]+ 165.08067 predictedDeepCCS 1.0 (2019) [M+Na]+ 183.0052984 predictedDarkChem Lite v0.1.0 [M+Na]+ 182.4973984 predictedDarkChem Lite v0.1.0 [M+Na]+ 171.1738 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Protein heterodimerization activity
- Specific Function
- This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Components:
| Name | UniProt ID |
|---|---|
| Alpha-1A adrenergic receptor | P35348 |
| Alpha-1B adrenergic receptor | P35368 |
| Alpha-1D adrenergic receptor | P25100 |
References
- Raja SN, Treede RD, Davis KD, Campbell JN: Systemic alpha-adrenergic blockade with phentolamine: a diagnostic test for sympathetically maintained pain. Anesthesiology. 1991 Apr;74(4):691-8. doi: 10.1097/00000542-199104000-00012. [Article]
- Goldstein I: Oral phentolamine: an alpha-1, alpha-2 adrenergic antagonist for the treatment of erectile dysfunction. Int J Impot Res. 2000 Mar;12 Suppl 1:S75-80. [Article]
- Traish A, Gupta S, Gallant C, Huang YH, Goldstein I: Phentolamine mesylate relaxes penile corpus cavernosum tissue by adrenergic and non-adrenergic mechanisms. Int J Impot Res. 1998 Dec;10(4):215-23. doi: 10.1038/sj.ijir.3900351. [Article]
- FDA Approved Drug Products: RYZUMVI (phentolamine ophthalmic solution) 0.75%, for topical ophthalmic use [Link]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Thioesterase binding
- Specific Function
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
Components:
| Name | UniProt ID |
|---|---|
| Alpha-2A adrenergic receptor | P08913 |
| Alpha-2B adrenergic receptor | P18089 |
| Alpha-2C adrenergic receptor | P18825 |
References
- Raja SN, Treede RD, Davis KD, Campbell JN: Systemic alpha-adrenergic blockade with phentolamine: a diagnostic test for sympathetically maintained pain. Anesthesiology. 1991 Apr;74(4):691-8. doi: 10.1097/00000542-199104000-00012. [Article]
- Goldstein I: Oral phentolamine: an alpha-1, alpha-2 adrenergic antagonist for the treatment of erectile dysfunction. Int J Impot Res. 2000 Mar;12 Suppl 1:S75-80. [Article]
- Traish A, Gupta S, Gallant C, Huang YH, Goldstein I: Phentolamine mesylate relaxes penile corpus cavernosum tissue by adrenergic and non-adrenergic mechanisms. Int J Impot Res. 1998 Dec;10(4):215-23. doi: 10.1038/sj.ijir.3900351. [Article]
- FDA Approved Drug Products: RYZUMVI (phentolamine ophthalmic solution) 0.75%, for topical ophthalmic use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Blocker
- General Function
- Voltage-gated potassium channel activity
- Specific Function
- This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage ...
- Gene Name
- KCNJ11
- Uniprot ID
- Q14654
- Uniprot Name
- ATP-sensitive inward rectifier potassium channel 11
- Molecular Weight
- 43540.375 Da
References
- Proks P, Ashcroft FM: Phentolamine block of KATP channels is mediated by Kir6.2. Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11716-20. doi: 10.1073/pnas.94.21.11716. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54