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 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.
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 can be synthesized by alkylation of 3-(4-methylanilino)phenol using 2-chloromethylimidazoline: