Phentolamine

Phentolamine (Regitine) is a reversible nonselective alpha-adrenergic antagonist.

Mechanism
Its primary action is vasodilation due to α1 blockade.

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

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

It also has usefulness in the treatment of cocaine induced hypertension, where one would generally avoid beta blockers and where calcium channel blockers are not effective. Beta-blockers (e.g. metoprolol) or combined alpha and beta adrenergic blocking agents (e.g. labetalol) should be avoided in patients with a history of cocaine abuse. They can cause an unopposed alpha-adrenergic mediated coronary vasoconstriction, causing the worsening of myocardial ischemia and hypertension. It is also used in the treatment of pheochromocytoma prior to the administration of beta blockers to avoid unopposed alpha-stimulation.

In this context it is probably most safely given by infusion since bolus doses have a propensity towards causing precipitous falls in blood pressure.

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.

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).

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. OraVerse has been shown to accelerate the reversal of the lingering soft-tissue numbness associated with the widely used anesthetic-vasoconstrictor combinations.

Chemistry
Phentolamine, 2-[[N-(3′-hydroxyphenyl)-para-toluidion]methyl]-2-imidazoline, is synthesized by alkylation of 3-(4-methylanilino)phenol using 2-chloromethylimidazoline.
 * K. Miescher, A. Marxer, E. Urech, (1950).
 * E. Urech, A. Marxer, K. Miescher, Helv. Chim. Acta, 33, 1386 (1950).