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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
SynonymLanguageCode
FentolaminaSpanishINN
PhentolaminGermanINN
PhentolamineFrenchINN
PhentolaminumLatinINN
VesomaxNot AvailableIS
Salts
Name/CAS Structure Properties
Phentolamine Mesylate
Thumb Not applicable DBSALT000980
Brand names
NameCompany
OraVerseSeptodont
RegitinNovartis
RegitinaNovartis
RegitineNovartis
RogitinePaladin
VigamedGrupo Cimed
Brand mixtures
Brand NameIngredients
AndroskatPhentolamine and Papaverine
InvicorpPhentolamine and Aviptadil
Categories
CAS number50-60-2
WeightAverage: 281.3523
Monoisotopic: 281.152812245
Chemical FormulaC17H19N3O
InChI KeyMRBDMNSDAVCSSF-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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassPhenols and Derivatives
Direct parentAminophenols
Alternative parentsToluenes; Tertiary Amines; Polyamines; Enols; Carboxamidines
Substituentstoluene; tertiary amine; amidine; enol; polyamine; carboxylic acid amidine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the aminophenols. These are organic compounds containing an amino group attached to a phenol.
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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
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
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 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Inhibitor 0.8931
CYP450 2C19 substrate Non-inhibitor 0.8454
CYP450 3A4 substrate 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
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
SolutionIntravenous
Tablet, extended releaseOral
Prices
Unit descriptionCostUnit
Phentolamine 5 mg vial84.0USDvial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States75757572005-04-212025-04-21
United States67646782001-05-112021-05-11
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point174.5 °CPhysProp
logP3.3Not Available
Predicted Properties
PropertyValueSource
water solubility2.72e-01 g/lALOGPS
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 area47.86ChemAxon
rotatable bond count4ChemAxon
refractivity84.25ChemAxon
polarizability31.37ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
PubChem Compound5775
PubChem Substance46506535
ChemSpider5571
BindingDB50008789
Therapeutic Targets DatabaseDAP000299
PharmGKBPA450926
IUPHAR502
Guide to Pharmacology502
Drug Product Database2243737
RxListhttp://www.rxlist.com/cgi/generic3/phentol.htm
Drugs.comhttp://www.drugs.com/cons/phentolamine-injection.html
WikipediaPhentolamine
ATC CodesC04AB01V03AB36
AHFS Codes
  • 12:16.00
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(73.3 KB)
Interactions
Drug Interactions
Drug
TadalafilTadalafil may enhance the hypotensive effect of Phentolamine. Monitor for hypotension during concomitant therapy.
TamsulosinConcomitant use of alpha1-adrenergic antagonists, Tamsulosin and Phentolamine, may result in additive antihypertensive effects. Combination therapy is not recommended.
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
VardenafilAdditive hypotensive effects of the PDE5 inhibitor, Vardenafil, and alpha1-blocker, Phentolamine, may occur. Monitor for hypotension during concomitant therapy.
Food InteractionsNot Available

Targets

1. Alpha-2A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Alpha-2A adrenergic receptor P08913 Details

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
  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
  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
  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
  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
  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
  7. Bylund DB: Subtypes of alpha 1- and alpha 2-adrenergic receptors. FASEB J. 1992 Feb 1;6(3):832-9. Pubmed
  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

2. Alpha-1A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Alpha-1A adrenergic receptor P35348 Details

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
  2. Bylund DB: Subtypes of alpha 1- and alpha 2-adrenergic receptors. FASEB J. 1992 Feb 1;6(3):832-9. Pubmed
  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

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11