Phentolamine

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Phentolamine
Phentolamine Structural Formulae.svg
Phentolamine-space-filling.png
Systematic (IUPAC) name
3-[(4,5-dihydro-1H-imidazol-2-ylmethyl)(4-methylphenyl)amino]phenol
Clinical data
Trade names Regitine
AHFS/Drugs.com Micromedex Detailed Consumer Information
Pregnancy cat. C (U.S.)
Legal status ?
Routes Usually IV or IM
Pharmacokinetic data
Metabolism Hepatic
Half-life 19 minutes
Identifiers
CAS number 50-60-2 YesY
ATC code C04AB01 V03AB36
PubChem CID 5775
IUPHAR ligand 502
DrugBank DB00692
ChemSpider 5571 YesY
UNII Z468598HBV YesY
KEGG D08362 YesY
ChEBI CHEBI:8081 N
ChEMBL CHEMBL597 YesY
Chemical data
Formula C17H19N3O 
Mol. mass 281.352 g/mol
 N (what is this?)  (verify)

Phentolamine (Regitine) is a reversible[1] nonselective alpha-adrenergic antagonist.[2]

Mechanism[edit]

Its primary action is vasodilation due to α1 blockade.[3]

It also can lead to reflex tachycardia because of hypotension and α2 inhibition, which increases sympathetic tone.[4]

Uses[edit]

The primary application for phentolamine is for the control of hypertensive emergencies, most notably due to pheochromocytoma. [5]

It also has usefulness in the treatment of cocaine-induced cardiovascular complications, where one would generally avoid Beta-blockers (e.g. metoprolol), as they can cause unopposed alpha-adrenergic mediated coronary vasoconstriction, worsening myocardial ischemia and hypertension. It is important to note that phentolamine is not a first-line agent for this indication. Phentolamine should only be given to patients who do not fully respond to benzodiazepines, nitroglycerin, and calcium channel blockers. [6][7]

When given by injection it causes blood vessels to expand, thereby increasing blood flow. When injected into the penis (intracavernosal), it increases blood flow to the penis, which results in an erection.[8]

It may be stored in crash carts to counteract severe peripheral vasoconstriction secondary to extravasation of peripherally placed vasopressor infusions, typically of norepinephrine. Epinephrine infusions are less vasoconstrictive than norepinephrine as they primarily stimulate beta receptor more than alpha receptors, but the effect remains dose dependent.

Phentolamine also has diagnostic and therapeutic roles in complex regional pain syndrome (reflex sympathetic dystrophy).[9]

Phentolamine has recently been introduced in the dental field as a local anesthetic reversal agent. Distributed by Septodont, OraVerse is a Phentolamine Mesylate injection designed to reverse the local vasoconstrictor properties used in many local anesthetics to prolong anesthesia.[10] OraVerse has been shown to accelerate the reversal of the lingering soft-tissue numbness associated with the widely used anesthetic-vasoconstrictor combinations.[11]

Chemistry[edit]

Phentolamine can be synthesized by alkylation of 3-(4-methylanilino)phenol using 2-chloromethylimidazoline:[12][13]

Phentolamine synthesis.png

References[edit]

  1. ^ Jewell, John R.; Longworth, David L.; Stoller, James K.; Casey, David (2003). The Cleveland Clinic internal medicine case reviews. Hagerstown, MD: Lippincott Williams & Wilkins. p. 32. ISBN 0-7817-4266-8. 
  2. ^ Phentolamine at the US National Library of Medicine Medical Subject Headings (MeSH)
  3. ^ Brock G. Oral phentolamine (Vasomax). Drugs Today (Barcelona). 2000 Feb-Mar;36(2-3):121-4.
  4. ^ Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 14. ISBN 1-59541-101-1. 
  5. ^ Tuncel M, Ram VC. Hypertensive emergencies. Etiology and management. American Journal of Cardiovascular Drugs. 2003;3(1):21-31.
  6. ^ Hollander JE, Henry TD. Evaluation and management of the patient who has cocaine-associated chest pain. Cardiology Clinics. 2006 Feb;24(1):103-14.
  7. ^ Chan GM, Sharma R, Price D, Hoffman RS, Nelson LS. Phentolamine Therapy for Cocaine-Association Acute Coronary Syndrome (CAACS). Journal of Medical Toxicology. 2006 Sep;2(3):108-11.
  8. ^ Bella AJ, Brock GB. Intracavernous pharmacotherapy for erectile dysfunction. Endocrine. 2004 Mar-Apr;23(2-3):149-55.
  9. ^ Rowbotham MC. Pharmacologic management of complex regional pain syndrome. Clinical Journal of Pain. 2006 Jun;22(5):425-9.
  10. ^ http://www.novalar.com/oraverse-dental-specialty-pharmaceutical
  11. ^ Malamed S. What's new in local anaesthesia? Society For The Advancement Of Anaesthesia In Dentistry Digest. 2009 Jan;25:4-14.
  12. ^ K. Miescher, A. Marxer, E. Urech, U.S. Patent 2,503,059 (1950)
  13. ^ E. Urech, A. Marxer, K. Miescher, Helv. Chim. Acta, 33, 1386 (1950)