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

adrenergic antagonist An adrenergic antagonist is a drug that inhibits the function of adrenergic receptors. There are five adrenergic receptors, which are divided into two groups. The first group of receptors are the beta (β) adrenergic receptors. There are β1, � ...

Mechanism

Its primary action is

vasodilation Vasodilation, also known as vasorelaxation, 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. Blood vessel wa ...

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, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...

. 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 cause ...

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

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

. In response, the β₁ adrenergic receptors on the heart increase their rate,

contractility Contractility refers to the ability for self- contraction, especially of the muscles or similar active biological tissue *Contractile ring in cytokinesis *Contractile vacuole *Muscle contraction **Myocardial contractility *See contractile cell fo ...

, 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 In the nervous system, a synapse is a structure that allows a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or a target effector cell. Synapses can be classified as either chemical or electrical, depending o ...

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

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, most notably due to

pheochromocytoma Pheochromocytoma is a rare tumor of the adrenal medulla composed of chromaffin cells and is part of the paraganglioma (PGL) family of tumors, being defined as an intra-adrenal PGL. These neuroendocrine tumors can be sympathetic, where they relea ...

. It also has usefulness in the treatment of

cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...

-induced cardiovascular complications, where one would generally avoid

β-blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms (arrhythmia), and to protect the heart from a second heart attack after a first heart attack (secondary prevention). ...

s (e.g.

metoprolol Metoprolol, sold under the brand name Lopressor among others, is a medication used to treat angina, high blood pressure and a number of conditions involving an abnormally fast heart rate. It is also used to prevent further heart problems afte ...

), 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

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...

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

, 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 Dilation (or dilatation) may refer to: Physiology or medicine * Cervical dilation, the widening of the cervix in childbirth, miscarriage etc. * Coronary dilation, or coronary reflex * Dilation and curettage, the opening of the cervix and surg ...

, 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, code cart, crash trolley 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 for life support protoc ...

s to counteract severe peripheral vasoconstriction secondary to

extravasation Extravasation is the leakage of a fluid out of its contained space into the surrounding area, especially blood or blood cells from vessels. In the case of inflammation, it refers to the movement of white blood cells through the capillary wall, ...

of peripherally placed

vasopressor An antihypotensive, also known as a vasopressor, is an agent that raises blood pressure by constricting blood vessels, thereby increasing systemic vascular resistance. This is different from inotropes which increase the force of cardiac contrac ...

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 a ...

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 type 1 and type 2), sometimes referred to by the hyponyms reflex sympathetic dystrophy (RSD) or reflex neurovascular dystrophy (RND), is a rare and severe form of neuroinflammatory and dysautonomic disorder ...

(CRPS). 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. Phentolamine is also used ophthalmically under the brand name Ryzumvi to reverse the effects of pharmacologically-induced

mydriasis Mydriasis is the Pupillary dilation, dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, Physical trauma, trauma, or the use of c ...

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 they are standing up ( orthostasis) or sitting down. Primary orthostatic hypotension is also often referred to as ne ...

References

{{Portal bar , Medicine Alpha-1 blockers Alpha-2 blockers Anilines Antihypertensive agents Disulfiram-like drugs Imidazolines 3-Hydroxyphenyl compounds Vasodilators 4-Tolyl compounds