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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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Phenotolamine
Phentalamine
Phentolamine Mesilate
Phentolamine Mesylate
Phentolamine Mesylate [USAN]
Phentolamine Methanesulfonate
Phentolamine Methanesulphonate
Phentolamine, Methyl Sulfonate
Regitin
Regitin Methanesulphonate
Regitine
Regitine Mesylate
Regitine Methanesulfonate
Regitipe
Rogitine
First Prev Next Last
Brand mixtures Not Available
Categories
  • Antihypertensive Agents
  • Sympatholytics
  • Adrenergic alpha-Antagonists
CAS number 50-60-2
Weight Average: 281.3523
Monoisotopic: 281.152812245
Chemical Formula C17H19N3O
InChI Key InChIKey=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)
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenols and Derivatives
  • Aminophenols and Derivatives
Substructures
  • Hydroxy Compounds
  • Imidazolines
  • Carboxylic Acids and Derivatives
  • Phenols and Derivatives
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Aminophenols and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamidines
  • Imines
  • Phenyl Esters
  • Anilines
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.
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.
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
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
Form Route Strength
Solution Intravenous
Tablet, extended release Oral
Prices
Unit description Cost Unit
Phentolamine 5 mg vial 84.0 USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 7575757 2005-04-21 2025-04-21
United States 6764678 2001-05-11 2021-05-11
Properties
State solid
Experimental Properties
Property Value Source
melting point 174.5 °C PhysProp
logP 3.3 Not Available
Predicted Properties
Property Value Source
water solubility 2.72e-01 g/l 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 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 84.25 ChemAxon
polarizability 31.37 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
PubChem Compound 5775 Link_out
PubChem Substance 46506535 Link_out
ChemSpider 5571 Link_out
BindingDB 50008789 Link_out
Therapeutic Targets Database DAP000299 Link_out
PharmGKB PA450926 Link_out
IUPHAR 502 Link_out
Guide to Pharmacology 502 Link_out
Drug Product Database 2243737 Link_out
RxList http://www.rxlist.com/cgi/generic3/phentol.htm Link_out
Drugs.com http://www.drugs.com/cons/phentolamine-injection.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Phentolamine Link_out
ATC Codes
  • C04AB01
  • V03AB36
AHFS Codes
  • 12:16.00
PDB Entries Not Available
FDA label Not Available
MSDS show (73.3 KB)
Interactions
Drug Interactions
Drug Interaction
Tadalafil Tadalafil may enhance the hypotensive effect of Phentolamine. Monitor for hypotension during concomitant therapy.
Tamsulosin Concomitant use of alpha1-adrenergic antagonists, Tamsulosin and Phentolamine, may result in additive antihypertensive effects. Combination therapy is not recommended.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Vardenafil Additive hypotensive effects of the PDE5 inhibitor, Vardenafil, and alpha1-blocker, Phentolamine, may occur. Monitor for hypotension during concomitant therapy.
Food Interactions Not Available
Targets

1. Alpha-2A adrenergic receptor

Pharmacological action: yes
Actions: antagonist

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 = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol

Organism class: human
UniProt ID: P08913 Link_out
Gene: ADRA2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: antagonist

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

Organism class: human
UniProt ID: P35348 Link_out
Gene: ADRA1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19