phentolamine

The primary application for phentolamine is for the control of hypertensive emergencies, most notably due to pheochromocytoma.{{cite journal | vauthors = Tuncel M, Ram VC | s2cid = 1993954 | title = Hypertensive emergencies. Etiology and management | journal = American Journal of Cardiovascular Drugs | volume = 3 | issue = 1 | pages = 21–31 | date = 2003 | pmid = 14727943 | doi = 10.2165/00129784-200303010-00003 }}

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.{{cite journal | vauthors = Schurr JW, Gitman B, Belchikov Y | title = Controversial therapeutics: the β-adrenergic antagonist and cocaine-associated cardiovascular complications dilemma | journal = Pharmacotherapy | volume = 34 | issue = 12 | pages = 1269–1281 | date = December 2014 | pmid = 25224512 | doi = 10.1002/phar.1486 | s2cid = 5282953 }}{{cite journal | vauthors = Freeman K, Feldman JA | title = Cocaine, myocardial infarction, and beta-blockers: time to rethink the equation? | journal = Annals of Emergency Medicine | volume = 51 | issue = 2 | pages = 130–134 | date = February 2008 | pmid = 17933425 | doi = 10.1016/j.annemergmed.2007.08.020 }} 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.{{cite journal | vauthors = Hollander JE, Henry TD | title = Evaluation and management of the patient who has cocaine-associated chest pain | journal = Cardiology Clinics | volume = 24 | issue = 1 | pages = 103–114 | date = February 2006 | pmid = 16326260 | doi = 10.1016/j.ccl.2005.09.003 }}{{cite journal | vauthors = Chan GM, Sharma R, Price D, Hoffman RS, Nelson LS | title = Phentolamine therapy for cocaine-association acute coronary syndrome (CAACS) | journal = Journal of Medical Toxicology | volume = 2 | issue = 3 | pages = 108–111 | date = September 2006 | pmid = 18072128 | pmc = 3550159 | doi = 10.1007/BF03161019 }}

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.{{cite journal | vauthors = Bella AJ, Brock GB | s2cid = 13056029 | title = Intracavernous pharmacotherapy for erectile dysfunction | journal = Endocrine | volume = 23 | issue = 2–3 | pages = 149–55 | date = 2004 | pmid = 15146094 | doi = 10.1385/ENDO:23:2-3:149 }}

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.

Phentolamine also has diagnostic and therapeutic roles in complex regional pain syndrome (CRPS).{{cite journal | vauthors = Rowbotham MC | s2cid = 17837280 | title = Pharmacologic management of complex regional pain syndrome | journal = The Clinical Journal of Pain | volume = 22 | issue = 5 | pages = 425–9 | date = June 2006 | pmid = 16772796 | doi = 10.1097/01.ajp.0000194281.74379.01 }}

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.{{cite journal | vauthors = Malamed S | title = What's new in local anaesthesia? | journal = SAAD Digest | volume = 25 | pages = 4–14 | date = January 2009 | pmid = 19267135 }}

Phentolamine is also used ophthalmically under the brand name Ryzumvi to reverse the effects of pharmacologically-induced mydriasis.{{Cite web |date=2023-09-27 |title=FDA approves RYZUMVI (Phentolamine Ophthalmic Solution) for the treatment of pharmacologically-induced mydriasis |url=https://www.ophthalmologytimes.com/view/fda-approves-ryzumvi-phentolamine-ophthalmic-solution-for-the-treatment-of-pharmacologically-induced-mydriasis |access-date=2025-02-21 |website=Ophthalmology Times |language=en}}

A possible adverse effect of phentolamine is orthostatic hypotension.{{cite web|url=http://www.rxlist.com/phentolamine-mesylate-for-injection-side-effects-drug-center.htm|title=Common Side Effects of Phentolamine Mesylate for Injection (Phentolamine Mesylate) | work = Drug Center - RxList }}

Phentolamine acts as a reversible dual or non-selective α₁- and α₂-adrenergic receptor antagonist.{{cite web | title=Phentolamine: Uses, Interactions, Mechanism of Action | website=DrugBank Online | date=1 June 2011 | url=https://go.drugbank.com/drugs/DB00692 | access-date=10 July 2025}} Its primary action is vasodilation due to α₁-adrenergic receptor blockade.{{cite journal | vauthors = Brock G | title = Oral phentolamine (Vasomax) | journal = Drugs of Today | location = Barcelona, Spain | volume = 36 | issue = 2–3 | pages = 121–4 | date = 2000 | pmid = 12879109 | doi = 10.1358/dot.2000.36.2-3.568785 }} Reportedly, phentolamine may also stimulate β-adrenergic receptors.{{cite journal | vauthors = Gould L, Reddy CV | title = Phentolamine | journal = Am Heart J | volume = 92 | issue = 3 | pages = 397–402 | date = September 1976 | pmid = 949032 | doi = 10.1016/s0002-8703(76)80121-4 | url = }}

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.{{cite book | vauthors = Shen H | title=Illustrated Pharmacology Memory Cards: PharMnemonics | year=2008 | publisher=Minireview | isbn=978-1-59541-101-3 | page=14}}

Phentolamine can be synthesized by alkylation of 3-(4-methylanilino)phenol using 2-chloromethylimidazoline:{{cite patent | inventor = Miescher K, Marxer A, Urech E | assign1 = Ciba Pharmaceuticals Products, Inc. | country = US | number = 2503059 | title = 2-(N:N-diphenyl-aminomethyl) imidazolines | gdate = 1950 }}{{cite journal | vauthors = Urech E, Marxer A, Miescher K | title = 2-Aminoalkylimidazoline. | journal = Helv. Chim. Acta | date = 1950 | volume = 33 | issue = 5 | pages = 1386–407 | doi = 10.1002/hlca.19500330539 }}

:File:Phentolamine synthesis.png{{clear left}}

{{reflist}}

{{Antihypertensives and diuretics}}

{{Peripheral vasodilators}}

{{Drugs for erectile dysfunction and PE}}

{{Alpha blockers}}

{{Portal bar | Medicine}}

Category:Alpha-1 blockers

Category:Alpha-2 blockers

Category:Anilines

Category:Antihypertensive agents

Category:Disulfiram-like drugs

Category:Imidazolines

Category:3-Hydroxyphenyl compounds

Category:Vasodilators

Category:4-Tolyl compounds