Phentolamine, sold under the brand name Regitine among others, is a reversible nonselective α- adrenergic antagonist.

Mechanism

Its primary action is

vasodilation Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstrictio ...

due to α₁ blockade. Non-selective α-blockers can cause a much more pronounced reflex

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...

than the selective α₁ blockers. Like the selective α₁ blockers, phentolamine causes a relaxation of systemic vasculature, leading to

hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the di ...

. This hypotension is sensed by the

baroreceptor reflex The baroreflex or baroreceptor reflex is one of the body's homeostatic mechanisms that helps to maintain blood pressure at nearly constant levels. The baroreflex provides a rapid negative feedback loop in which an elevated blood pressure causes th ...

, which results in increased sympathetic nerve firing on the heart, releasing

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad ...

. 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 Negative feedback (or balancing feedback) occurs when some function of the output of a system, process, or mechanism is fed back in a manner that tends to reduce the fluctuations in the output, whether caused by changes in the input or by othe ...

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.

Uses

The primary application for phentolamine is for the control of

hypertensive emergencies A hypertensive emergency is very high blood pressure with potentially life-threatening symptoms and signs of acute damage to one or more organ systems (especially brain, eyes, heart, aorta, or kidneys). It is different from a hypertensive urgency ...

, most notably due to

pheochromocytoma Pheochromocytoma (PHEO or PCC) is a rare tumor of the adrenal medulla composed of chromaffin cells, also known as pheochromocytes. When a tumor composed of the same cells as a pheochromocytoma develops outside the adrenal gland, it is referred t ...

. It also has usefulness in the treatment of

cocaine Cocaine (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Am ...

-induced cardiovascular complications, where one would generally avoid β-blockers (e.g.

metoprolol Metoprolol, sold under the brand name Lopressor, among others, is a selective β1 receptor blocker medication. It is used to treat high blood pressure, chest pain due to poor blood flow to the heart, and a number of conditions involving an a ...

), as they can cause unopposed α-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

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...

nitroglycerin Nitroglycerin (NG), (alternative spelling of nitroglycerine) also known as trinitroglycerin (TNG), nitro, glyceryl trinitrate (GTN), or 1,2,3-trinitroxypropane, is a dense, colorless, oily, explosive liquid most commonly produced by nitrating g ...

, and

calcium channel blocker Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...

s. 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. It may be stored in

crash cart A crash cart or code cart (crash trolley in UK medical jargon) or "MAX cart" is a set of trays/drawers/shelves on wheels used in hospitals for transportation and dispensing of emergency medication/equipment at site of medical/surgical emergency ...

s to counteract severe peripheral vasoconstriction secondary to extravasation of peripherally placed

vasopressor An antihypotensive agent, also known as a vasopressor agent or simply vasopressor, or pressor, is any substance, whether endogenous or a medication, that tends to raise low blood pressure. Some antihypotensive drugs act as vasoconstrictors to i ...

infusions, typically of

Epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...

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 Complex regional pain syndrome (CRPS) is any of several painful conditions that are characterized by a continuing (spontaneous and/or evoked) regional pain that is seemingly disproportionate in time or degree to the usual course of any known trau ...

(reflex sympathetic dystrophy). 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.

Chemistry

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

Adverse effects

Orthostatic hypotension Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when standing up or sitting down. Primary orthostatic hypertension is also often referred to as neurogenic orthostatic hyp ...

References

External links

* {{Portal bar , Medicine Alpha-1 blockers Alpha-2 blockers Anilines Antihypertensive agents Disulfiram-like drugs Imidazolines Phenols Vasodilators 4-Tolyl compounds