Phentolamine

Overview

Phentolamine, sold under the brand name Regitine among others, is a non-selective α-adrenergic antagonist.[1][2] WP

Uses, dosage and effects

Medical uses

The primary application for phentolamine is for the control of hypertensive emergencies, most notably due to pheochromocytoma.[3] WP

It also has usefulness in the treatment of cocaine-induced cardiovascular complications, where one would generally avoid β-blockers (e.g., metoprolol), as they can cause unopposed α-adrenergic mediated coronary vasoconstriction, worsening myocardial ischemia and hypertension. 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.[4–7] WP

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

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 β receptor more than α receptors, but the effect remains dose-dependent. WP

Phentolamine also has diagnostic and therapeutic roles in complex regional pain syndrome (CRPS).[9] WP

Phentolamine is marketed in the dental field as a local anesthetic reversal agent. Branded as OraVerse, it is a phentolamine mesylate injection designed to reverse the local vasoconstrictor properties used in many local anesthetics to prolong anesthesia.[10] WP

Phentolamine is also used ophthalmically under the brand name Ryzumvi to reverse the effects of pharmacologically-induced mydriasis.[11] WP

Risks and side effects

Side effects

A possible adverse effect of phentolamine is orthostatic hypotension.[12] WP

Pharmacology

Mechanism of action

Phentolamine acts as a reversible dual or non-selective α₁- and α₂-adrenergic receptor antagonist. Its primary action is vasodilation due to α₁-adrenergic receptor blockade. Reportedly, phentolamine may also stimulate β-adrenergic receptors.[2][13][14][15] WP

Non-selective α-blockers can cause a much more pronounced reflex tachycardia than the selective α₁ blockers. Like the selective α₁ blockers, phentolamine causes a relaxation of systemic vasculature, leading to hypotension. This hypotension is sensed by the baroreceptor reflex, which results in increased sympathetic nerve firing on the heart, releasing norepinephrine. In response, the β₁ adrenergic receptors on the heart increase their rate, contractility, and dromotropy, which help to offset the decrease in systemic blood pressure. Unlike the α₁ selective blockers, phentolamine also inhibits the α₂ receptors, which function predominantly as presynaptic negative feedback for norepinephrine release. By abolishing this negative feedback phentolamine leads to even less regulated norepinephrine release, which results in a more drastic increase in heart rate.[16] WP

Chemistry

Formula

C17H19N3O PC

CAS number

50-60-2 PC

Molar mass (g/mol)

281.35 PC

IUPAC name (computed by PubChem)

3-[N-(4,5-dihydro-1H-imidazol-2-ylmethyl)-4-methylanilino]phenol PC

SMILES

CC1=CC=C(C=C1)N(CC2=NCCN2)C3=CC(=CC=C3)O PC

InChIKey

MRBDMNSDAVCSSF-UHFFFAOYSA-N PC

PubChem CID

5775

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other MeshName Phentolamine
2. Other Jewell JR, Longworth DL, Stoller JK, Casey D. The Cleveland Clinic internal medicine case reviews. 2003
3. Journal / agency Tuncel M, Ram VC. Hypertensive emergencies. Etiology and management. American Journal of Cardiovascular Drugs. 2003. doi:10.2165/00129784-200303010-00003 · PMID 14727943
4. Journal / agency Schurr JW, Gitman B, Belchikov Y. Controversial therapeutics: the β-adrenergic antagonist and cocaine-associated cardiovascular complications dilemma. Pharmacotherapy. December 2014. doi:10.1002/phar.1486 · PMID 25224512
5. Journal / agency Freeman K, Feldman JA. Cocaine, myocardial infarction, and beta-blockers: time to rethink the equation?. Annals of Emergency Medicine. February 2008. doi:10.1016/j.annemergmed.2007.08.020 · PMID 17933425
6. Journal / agency Hollander JE, Henry TD. Evaluation and management of the patient who has cocaine-associated chest pain. Cardiology Clinics. February 2006. doi:10.1016/j.ccl.2005.09.003 · PMID 16326260
7. Journal / agency Chan GM, Sharma R, Price D, Hoffman RS, Nelson LS. Phentolamine therapy for cocaine-association acute coronary syndrome (CAACS). Journal of Medical Toxicology. September 2006. doi:10.1007/BF03161019 · PMID 18072128 · PMC3550159
8. Journal / agency Bella AJ, Brock GB. Intracavernous pharmacotherapy for erectile dysfunction. Endocrine. 2004. doi:10.1385/ENDO:23:2-3:149 · PMID 15146094
9. Journal / agency Rowbotham MC. Pharmacologic management of complex regional pain syndrome. The Clinical Journal of Pain. June 2006. doi:10.1097/01.ajp.0000194281.74379.01 · PMID 16772796
10. Journal / agency Malamed S. What's new in local anaesthesia?. SAAD Digest. January 2009. PMID 19267135
11. Other FDA approves RYZUMVI (Phentolamine Ophthalmic Solution) for the treatment of pharmacologically-induced mydriasis. 2023-09-27
12. Other Common Side Effects of Phentolamine Mesylate for Injection (Phentolamine Mesylate)
13. Harm reduction site Phentolamine: Uses, Interactions, Mechanism of Action. 1 June 2011
14. Journal / agency Brock G. Oral phentolamine (Vasomax). Drugs of Today. 2000. doi:10.1358/dot.2000.36.2-3.568785 · PMID 12879109
15. Journal / agency Gould L, Reddy CV. Phentolamine. Am Heart J. September 1976. doi:10.1016/s0002-8703(76)80121-4 · PMID 949032
16. Other Shen H. Illustrated Pharmacology Memory Cards: PharMnemonics. 2008

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.