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Identification
NamePhentolamine
Accession NumberDB00692  (APRD00615)
TypeSmall Molecule
GroupsApproved
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
Phentolamine mesylate
Phentolaminum
Regitina
Regitine
Rogitine
Vesomax
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Oraverseinjection, solution.235 mg/mLsubmucosalSeptodont, Inc.2011-06-01Not applicableUs
Oraversesolution0.4 mgsubmucosalSeptodont2014-09-17Not applicableCanada
Phentolamine Mesylate Injection Sandoz Standardsolution5 mgintramuscular; intravenousSandoz Canada Incorporated2001-06-15Not applicableCanada
Rogitinesolution10 mgintramuscular; intravenousPaladin Labs Inc2000-12-18Not applicableCanada
Rogitine 5mg/vialpowder for solution5 mgintramuscular; intravenousNovartis Pharmaceuticals Canada Inc1953-12-312000-08-02Canada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Phentolamine Mesylateinjection, powder, for solution5 mg/mLintramuscular; intravenousWest Ward Pharmaceuticals Corp1998-05-15Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
RegitinNovartis
RegitinaNovartis
RegitineNovartis
VigamedGrupo Cimed
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Phentolamine Mesylate
ThumbNot applicableDBSALT000980
Categories
UNIIZ468598HBV
CAS number50-60-2
WeightAverage: 281.3523
Monoisotopic: 281.152812245
Chemical FormulaC17H19N3O
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganonitrogen compounds
ClassAmines
Sub ClassTertiary amines
Direct ParentAlkyldiarylamines
Alternative Parents
Substituents
  • Alkyldiarylamine
  • Aminotoluene
  • Substituted aniline
  • Aminophenol
  • Toluene
  • Phenol
  • Aniline
  • Imidolactam
  • Benzenoid
  • Monocyclic benzene moiety
  • 2-imidazoline
  • Azacycle
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboximidamide
  • Carboxylic acid amidine
  • Amidine
  • Hydrocarbon derivative
  • Organooxygen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationUsed 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.
PharmacodynamicsPhentolamine 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 actionPhentolamine 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of elimination10-13% of the drug is excreted unchanged in urine, and the fate of the remainder of the drug is unknown.
Half life19 minutes
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
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
Dosage forms
FormRouteStrength
Injection, solutionsubmucosal.235 mg/mL
Solutionsubmucosal0.4 mg
Injection, powder, for solutionintramuscular; intravenous5 mg/mL
Solutionintramuscular; intravenous5 mg
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)
US6764678 No2001-05-112021-05-11Us
US6872390 No2001-05-112021-05-11Us
US7229630 No2003-06-202023-06-20Us
US7569230 No2003-10-172023-10-17Us
US7575757 No2005-04-212025-04-21Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point174.5 °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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesC04AB01V03AB36
AHFS Codes
  • 12:16.00
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (73.3 KB)
Interactions
Drug Interactions
Drug
AlfuzosinAlfuzosin may increase the antihypertensive activities of Phentolamine.
AmifostinePhentolamine may increase the hypotensive activities of Amifostine.
AmlodipinePhentolamine may increase the hypotensive activities of Amlodipine.
AmrinonePhentolamine may increase the hypotensive activities of Amrinone.
BepridilPhentolamine may increase the hypotensive activities of Bepridil.
BrimonidineBrimonidine may increase the antihypertensive activities of Phentolamine.
DapoxetineDapoxetine may increase the orthostatic hypotensive activities of Phentolamine.
DiazoxideDiazoxide may increase the hypotensive activities of Phentolamine.
DipivefrinPhentolamine may decrease the vasoconstricting activities of Dipivefrin.
FelodipinePhentolamine may increase the hypotensive activities of Felodipine.
FlunarizinePhentolamine may increase the hypotensive activities of Flunarizine.
GabapentinPhentolamine may increase the hypotensive activities of Gabapentin.
IsradipinePhentolamine may increase the hypotensive activities of Isradipine.
LamotriginePhentolamine may increase the hypotensive activities of Lamotrigine.
LercanidipinePhentolamine may increase the hypotensive activities of Lercanidipine.
Magnesium SulfatePhentolamine may increase the hypotensive activities of Magnesium Sulfate.
MethylphenidateMethylphenidate may decrease the antihypertensive activities of Phentolamine.
MidodrinePhentolamine may decrease the vasoconstricting activities of Midodrine.
MolsidomineMolsidomine may increase the hypotensive activities of Phentolamine.
MoxonidineMoxonidine may increase the hypotensive activities of Phentolamine.
NadololNadolol may increase the orthostatic hypotensive activities of Phentolamine.
NicardipinePhentolamine may increase the hypotensive activities of Nicardipine.
NimodipinePhentolamine may increase the hypotensive activities of Nimodipine.
NisoldipinePhentolamine may increase the hypotensive activities of Nisoldipine.
NitrendipinePhentolamine may increase the hypotensive activities of Nitrendipine.
ObinutuzumabPhentolamine may increase the hypotensive activities of Obinutuzumab.
PentoxifyllinePentoxifylline may increase the hypotensive activities of Phentolamine.
PerhexilinePhentolamine may increase the hypotensive activities of Perhexiline.
PhenelzinePhenelzine may increase the orthostatic hypotensive activities of Phentolamine.
PrazosinPrazosin may increase the antihypertensive activities of Phentolamine.
PrenylaminePhentolamine may increase the hypotensive activities of Prenylamine.
QuinineQuinine may increase the hypotensive activities of Phentolamine.
RisedronatePhentolamine may increase the hypotensive activities of Risedronate.
RituximabPhentolamine may increase the hypotensive activities of Rituximab.
TadalafilTadalafil may increase the hypotensive activities of Phentolamine.
TranylcypromineTranylcypromine may increase the orthostatic hypotensive activities of Phentolamine.
TreprostinilTreprostinil may increase the hypotensive activities of Phentolamine.
VardenafilVardenafil may increase the hypotensive activities of Phentolamine.
VerapamilPhentolamine may increase the hypotensive activities of Verapamil.
YohimbineYohimbine may decrease the antihypertensive activities of Phentolamine.
Food InteractionsNot Available

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 oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianser...
Gene Name:
ADRA2A
Uniprot ID:
P08913
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) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1A
Uniprot ID:
P35348
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 ]
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Drug created on June 13, 2005 07:24 / Updated on June 29, 2016 01:51