Identification

Name
Phentolamine
Accession Number
DB00692  (APRD00615)
Type
Small Molecule
Groups
Approved
Description

A nonselective alpha-adrenergic antagonist. It is used in the treatment of hypertension and hypertensive emergencies, pheochromocytoma, vasospasm of raynaud disease and frostbite, clonidine withdrawal syndrome, impotence, and peripheral vascular disease. [PubChem]

Structure
Thumb
Synonyms
  • 2-(N-(m-Hydroxyphenyl)-P-toluidinomethyl)imidazoline
  • Fentolamina
  • Phentolamin
  • Phentolamine
  • Phentolaminum
  • Regitina
  • Vesomax
Product Ingredients
IngredientUNIICASInChI Key
Phentolamine MesylateY7543E5K9TNot AvailableNot applicable
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
OraverseSolution0.4 mgSubmucosalSeptodont2014-09-17Not applicableCanada
OraverseInjection, solution0.235 mg/1mLSubmucosalSeptodont2011-06-01Not applicableUs
OraVerseInjection, solution0.4 mg/1.7mLSubmucosalNovalar Pharmaceuticals2008-05-23Not applicableUs
Phentolamine Mesylate Injection Sandoz StandardSolution5 mgIntramuscular; IntravenousSandoz Canada Incorporated2001-06-15Not applicableCanada
RegitineInjection, powder, lyophilized, for suspension5 mg/1mLIntramuscular; IntravenousUNSPECIFIED2006-05-10Not applicableUs
RogitineSolution10 mgIntramuscular; IntravenousPaladin Labs Inc2000-12-18Not applicableCanada
Rogitine 5mg/vialPowder, for solution5 mgIntramuscular; IntravenousNovartis1953-12-31Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Phentolamine MesylateInjection5 mg/1Intramuscular; IntravenousPrecision Dose, Inc.2017-07-15Not applicableUs
Phentolamine MesylateInjection, powder, for solution5 mg/1mLIntramuscular; IntravenousBedford Pharmaceuticals1998-05-152015-09-30Us
Phentolamine MesylateInjection5 mg/1Intramuscular; IntravenousTAGI Pharma, Inc.2017-07-15Not applicableUs
Phentolamine MesylateInjection, powder, for solution5 mg/1mLIntramuscular; IntravenousWest-Ward Pharmaceuticals Corp1998-05-15Not applicableUs
International/Other Brands
Regitin (Novartis) / Regitina (Novartis) / Regitine (Novartis) / Rogitine / Vigamed (Grupo Cimed)
Categories
UNII
Z468598HBV
CAS number
50-60-2
Weight
Average: 281.3523
Monoisotopic: 281.152812245
Chemical Formula
C17H19N3O
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-ylmethyl)(4-methylphenyl)amino]phenol
SMILES
CC1=CC=C(C=C1)N(CC1=NCCN1)C1=CC(O)=CC=C1

Pharmacology

Indication

Used as an aid for the diagnosis of pheochromocytoma, and may be administered immediately prior to or during pheochromocytomectomy to prevent or control paroxysmal hypertension resulting from anesthesia, stress, or operative manipulation of the tumor. Phentolamine has also been used to treat hypertensive crisis caused by sympathomimetic amines or catecholamine excess by certain foods or drugs in patients taking MAO inhibitors, or by clonidine withdrawal syndrome. Other indications include the prevention of dermal necrosis and sloughing following IV administration or extravasation of norepinephrine, decrease in impedance to left ventricular ejection and the infarct size in patients with MI associated with left ventricular failure, treatment of erectile dysfunction through self-injection of small doses combined with papaverine hydrochloride into the corpus cavernosum, and as an adjunct to the management of cocaine overdose to reverse coronary vasoconstriction following use of oxygen, benzodiazepines,and nitroglycerin.

Associated Conditions
Associated Therapies
Pharmacodynamics

Phentolamine is indicated for the control of episodes of hypertension and sweating that occur with a disease called pheochromocytoma. If tachycardia is excessive, it may be necessary to use a beta-blocking agent concomitantly. Phentolamine is a long-acting, adrenergic, alpha-receptor blocking agent which 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. Phentolamine works by blocking alpha receptors in certain parts of the body. Alpha receptors are present in the muscle that lines the walls of blood vessels. When the receptors are blocked by Phentolamine, the muscle relaxes and the blood vessels widen. This widening of the blood vessels results in a lowering of blood pressure.

Mechanism of action

Phentolamine produces its therapeutic actions by competitively blocking alpha-adrenergic receptors (primarily excitatory responses of smooth muscle and exocrine glands), 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. The action of phentolamine on the alpha adrenergic receptors is relatively transient and the blocking effect is incomplete. The drug is more effective in antagonizing responses to circulating epinephrine and/or norepinephrine than in antagonizing responses to mediator released at the adrenergic nerve ending. Phentolamine also stimulates β-adrenergic receptors and produces a positive inotropic and chronotropic effect on the heart and increases cardiac output.

TargetActionsOrganism
AAlpha-2A adrenergic receptor
antagonist
Human
AAlpha-1A adrenergic receptor
antagonist
Human
UAlpha-1B adrenergic receptor
antagonist
Human
UAlpha-1D adrenergic receptor
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

10-13% of the drug is excreted unchanged in urine, and the fate of the remainder of the drug is unknown.

Half life

19 minutes

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
4-MethoxyamphetamineThe therapeutic efficacy of 4-Methoxyamphetamine can be decreased when used in combination with Phentolamine.
AbacavirPhentolamine may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbediterolThe therapeutic efficacy of Abediterol can be decreased when used in combination with Phentolamine.
AcarboseAcarbose may decrease the excretion rate of Phentolamine which could result in a higher serum level.
AcebutololAcebutolol may increase the orthostatic hypotensive activities of Phentolamine.
AceclofenacThe therapeutic efficacy of Phentolamine can be decreased when used in combination with Aceclofenac.
AcemetacinThe therapeutic efficacy of Phentolamine can be decreased when used in combination with Acemetacin.
AcepromazinePhentolamine may increase the orthostatic hypotensive, hypotensive, and antihypertensive activities of Acepromazine.
AcetaminophenAcetaminophen may decrease the excretion rate of Phentolamine which could result in a higher serum level.
Acetylsalicylic acidThe therapeutic efficacy of Phentolamine can be decreased when used in combination with Acetylsalicylic acid.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014830
PubChem Compound
5775
PubChem Substance
46506535
ChemSpider
5571
BindingDB
31046
ChEBI
8081
ChEMBL
CHEMBL597
Therapeutic Targets Database
DAP000299
PharmGKB
PA450926
IUPHAR
502
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Phentolamine
ATC Codes
V03AB36 — PhentolamineC04AB01 — Phentolamine
AHFS Codes
  • 12:16.04.04 — Non-selective Alfa-adrenergic Blocking Agents
  • 12:16.00 — Sympatholytic (Adrenergic Blocking) Agents
MSDS
Download (73.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingBasic ScienceHypoglycemia / Hypoglycemia Unawareness / Type1diabetes1
1RecruitingBasic ScienceBMI >30 kg/m2 / Healthy Volunteers / Insulin Resistance1
1RecruitingBasic ScienceCardiovascular System Disease / Drug-Related Side Effects and Adverse Reactions1
1RecruitingBasic ScienceChronic Obstructive Pulmonary Disease (COPD) / Heart Failure, Unspecified / High Blood Pressure (Hypertension) / Pulmonary Arterial Hypertension (PAH)1
2CompletedSupportive CareProstate Cancer1
2CompletedTreatmentAnesthesia, Dental1
2CompletedTreatmentNight Vision Complaints1
2CompletedTreatmentSoft Tissue Anesthesia (Numbness)1
3CompletedTreatmentAnesthesia, Dental2
4CompletedTreatmentAnesthesia, Dental / Anesthesia, Reversal / Local Anesthesia1
4RecruitingTreatmentLocal Anesthesia1
Not AvailableCompletedTreatmentCVA (Cerebrovascular Accident) / Intracerebral Hemorrhage / Intracranial Hemorrhages1
Not AvailableCompletedTreatmentSoft Tissue Anaesthesia1
Not AvailableUnknown StatusNot AvailableCongestive Heart Failure (CHF)1

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
FormRouteStrength
Injection, solutionSubmucosal0.235 mg/1mL
Injection, solutionSubmucosal0.4 mg/1.7mL
SolutionSubmucosal0.4 mg
InjectionIntramuscular; Intravenous5 mg/1
Injection, powder, for solutionIntramuscular; Intravenous5 mg/1mL
SolutionIntramuscular; Intravenous5 mg
Injection, powder, lyophilized, for suspensionIntramuscular; Intravenous5 mg/1mL
SolutionIntramuscular; Intravenous10 mg
Powder, for solutionIntramuscular; Intravenous5 mg
Prices
Unit descriptionCostUnit
Phentolamine 5 mg vial84.0USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6764678No2001-05-112021-05-11Us
US7569230No2003-10-172023-10-17Us
US6872390No2001-05-112021-05-11Us
US7229630No2003-06-202023-06-20Us
US7575757No2005-04-212025-04-21Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)174.5 °CPhysProp
logP3.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.272 mg/mLALOGPS
logP2.91ALOGPS
logP2.52ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)9.78ChemAxon
pKa (Strongest Basic)9.02ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area47.86 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity84.25 m3·mol-1ChemAxon
Polarizability31.37 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9293
Blood Brain Barrier+0.838
Caco-2 permeable-0.6104
P-glycoprotein substrateSubstrate0.772
P-glycoprotein inhibitor INon-inhibitor0.9329
P-glycoprotein inhibitor IIInhibitor0.8031
Renal organic cation transporterInhibitor0.7497
CYP450 2C9 substrateNon-substrate0.6892
CYP450 2D6 substrateNon-substrate0.5668
CYP450 3A4 substrateNon-substrate0.6313
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.8454
CYP450 3A4 inhibitorNon-inhibitor0.831
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7661
Ames testNon AMES toxic0.6266
CarcinogenicityNon-carcinogens0.8555
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.4366 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.6149
hERG inhibition (predictor II)Inhibitor0.59
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03di-4890000000-37817fa5f0f18f71350d

Taxonomy

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
Alkyldiarylamine / M-aminophenol / Aminophenol / Aminotoluene / Aniline or substituted anilines / 1-hydroxy-4-unsubstituted benzenoid / 1-hydroxy-2-unsubstituted benzenoid / Phenol / Toluene / Monocyclic benzene moiety
show 15 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
tertiary amino compound, substituted aniline, imidazoles, phenols (CHEBI:8081)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
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...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
Molecular Weight
48956.275 Da
References
  1. Polak J, Moro C, Klimcakova E, Hejnova J, Majercik M, Viguerie N, Langin D, Lafontan M, Stich V, Berlan M: Dynamic strength training improves insulin sensitivity and functional balance between adrenergic alpha 2A and beta pathways in subcutaneous adipose tissue of obese subjects. Diabetologia. 2005 Dec;48(12):2631-40. Epub 2005 Nov 5. [PubMed:16273345]
  2. Molderings GJ, Bonisch H, Bruss M, Likungu J, Gothert M: Species-specific pharmacological properties of human alpha(2A)-adrenoceptors. Hypertension. 2000 Sep;36(3):405-10. [PubMed:10988273]
  3. Vonend O, Habbel S, Stegbauer J, Roth J, Hein L, Rump LC: Alpha(2A)-adrenoceptors regulate sympathetic transmitter release in mice kidneys. Br J Pharmacol. 2007 Jan;150(1):121-7. Epub 2006 Nov 20. [PubMed:17115069]
  4. Trendelenburg AU, Meyer A, Klebroff W, Guimaraes S, Starke K: Crosstalk between presynaptic angiotensin receptors, bradykinin receptors and alpha 2-autoreceptors in sympathetic neurons: a study in alpha 2-adrenoceptor-deficient mice. Br J Pharmacol. 2003 Apr;138(8):1389-402. [PubMed:12721093]
  5. Blandizzi C, Fornai M, Colucci R, Baschiera F, Barbara G, De Giorgio R, De Ponti F, Breschi MC, Del Tacca M: Altered prejunctional modulation of intestinal cholinergic and noradrenergic pathways by alpha2-adrenoceptors in the presence of experimental colitis. Br J Pharmacol. 2003 May;139(2):309-20. [PubMed:12770936]
  6. Giussani DA, Moore PJ, Bennet L, Spencer JA, Hanson MA: Alpha 1- and alpha 2-adrenoreceptor actions of phentolamine and prazosin on breathing movements in fetal sheep in utero. J Physiol. 1995 Jul 1;486 ( Pt 1):249-55. [PubMed:7562640]
  7. Bylund DB: Subtypes of alpha 1- and alpha 2-adrenergic receptors. FASEB J. 1992 Feb 1;6(3):832-9. [PubMed:1346768]
  8. Saeed M, Sommer O, Holtz J, Bassenge E: Alpha-adrenoceptor blockade by phentolamine causes beta-adrenergic vasodilation by increased catecholamine release due to presynaptic alpha-blockade. J Cardiovasc Pharmacol. 1982 Jan-Feb;4(1):44-52. [PubMed:6176798]
Kind
Protein
Organism
Human
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...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Giussani DA, Moore PJ, Bennet L, Spencer JA, Hanson MA: Alpha 1- and alpha 2-adrenoreceptor actions of phentolamine and prazosin on breathing movements in fetal sheep in utero. J Physiol. 1995 Jul 1;486 ( Pt 1):249-55. [PubMed:7562640]
  2. Bylund DB: Subtypes of alpha 1- and alpha 2-adrenergic receptors. FASEB J. 1992 Feb 1;6(3):832-9. [PubMed:1346768]
  3. Saeed M, Sommer O, Holtz J, Bassenge E: Alpha-adrenoceptor blockade by phentolamine causes beta-adrenergic vasodilation by increased catecholamine release due to presynaptic alpha-blockade. J Cardiovasc Pharmacol. 1982 Jan-Feb;4(1):44-52. [PubMed:6176798]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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...
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. Koshimizu TA, Tsujimoto G, Hirasawa A, Kitagawa Y, Tanoue A: Carvedilol selectively inhibits oscillatory intracellular calcium changes evoked by human alpha1D- and alpha1B-adrenergic receptors. Cardiovasc Res. 2004 Sep 1;63(4):662-72. [PubMed:15306222]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Alpha1-adrenergic receptor activity
Specific Function
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name
ADRA1D
Uniprot ID
P25100
Uniprot Name
Alpha-1D adrenergic receptor
Molecular Weight
60462.205 Da
References
  1. Koshimizu TA, Tsujimoto G, Hirasawa A, Kitagawa Y, Tanoue A: Carvedilol selectively inhibits oscillatory intracellular calcium changes evoked by human alpha1D- and alpha1B-adrenergic receptors. Cardiovasc Res. 2004 Sep 1;63(4):662-72. [PubMed:15306222]
  2. Zhang D, Yuan B, Deng X, Yang G, He L, Zhang Y, Han Q: Chromatography studies on bio-affinity of nine ligands of alpha1-adrenoceptor to alpha1D subtypes overexpressed in cell membrane. Sci China C Life Sci. 2004 Aug;47(4):376-81. [PubMed:15493479]

Drug created on June 13, 2005 07:24 / Updated on November 14, 2018 12:45