Phentolamine

Nonselective alpha-adrenergic antagonist

Phentolamine
INN
Drug class
Routes of administration	Intravenous, Intramuscular, Intracavernosal
Pregnancy category
Bioavailability
Metabolism	Liver
Elimination half-life	~19 minutes
Excretion	Urine
Legal status
CAS Number	50-60-2
PubChem	4757
DrugBank	DB00692
ChemSpider
KEGG

Phentolamine (brand names: Regitine, OraVerse) is a nonselective alpha-adrenergic antagonist used primarily in the management of hypertensive emergencies, pheochromocytoma, and erectile dysfunction.<ref name="isbn0-7817-4266-8">{{{last}}},

 Jewell, John R.; Longworth, David L.; Stoller, James K.; Casey, David, 
  
 The Cleveland Clinic Internal Medicine Case Reviews, 
  
 Lippincott Williams & Wilkins, 
 2003, 
  
  
 ISBN 0-7817-4266-8,</ref> It works by blocking alpha receptors, leading to vasodilation and a subsequent decrease in blood pressure.

Mechanism of Action

Phentolamine acts as a competitive, reversible alpha-adrenergic antagonist, blocking both α₁ and α₂ receptors:

• α₁ receptor blockade: Causes vasodilation, reducing vascular resistance and blood pressure.<ref>Brock G. Oral phentolamine (Vasomax). Drugs Today (Barcelona). 2000 Feb-Mar;36(2-3):121-4.</ref>
• α₂ receptor blockade: Inhibits negative feedback on norepinephrine release, leading to increased sympathetic activity, which may cause reflex tachycardia.<ref name=pharmnemonics>{{{last}}},

 Shen, Howard, 
  
 Illustrated Pharmacology Memory Cards: PharMnemonics, 
  
 Minireview, 
 2008, 
  
  
 ISBN 1-59541-101-1,</ref>

Therapeutic Uses

Phentolamine is utilized in various clinical scenarios, including:

1. Hypertensive Emergencies

• Used in pheochromocytoma crises to rapidly lower blood pressure.<ref>Tuncel M, Ram VC. Hypertensive emergencies. American Journal of Cardiovascular Drugs. 2003;3(1):21-31.</ref>
• Preferred in cocaine-induced hypertension, where beta-blockers are contraindicated to avoid unopposed α-adrenergic stimulation.

2. Pheochromocytoma Treatment

• Administered before beta-blockers to prevent hypertensive crises.

3. Erectile Dysfunction (ED)

• When injected intracavernosally, phentolamine increases penile blood flow, aiding erection induction.<ref>Bella AJ, Brock GB. Intracavernous pharmacotherapy for erectile dysfunction. Endocrine. 2004 Mar-Apr;23(2-3):149-55.</ref>

4. Peripheral Vasoconstriction Reversal

• Used in cases of extravasation of vasopressors (e.g., norepinephrine, dopamine), preventing tissue necrosis.

5. Complex Regional Pain Syndrome (CRPS)

• Phentolamine infusion can help diagnose and manage CRPS (Reflex Sympathetic Dystrophy).<ref>Rowbotham MC. Pharmacologic management of complex regional pain syndrome. Clinical Journal of Pain. 2006 Jun;22(5):425-9.</ref>

6. Local Anesthetic Reversal

• Marketed as OraVerse, phentolamine is used in dentistry to reverse local anesthetic effects, restoring normal sensation more quickly.<ref>http://www.novalar.com/oraverse-dental-specialty-pharmaceutical</ref>

Chemical Synthesis

Phentolamine's full chemical name is 2-[[N-(3′-hydroxyphenyl)-para-toluidino]methyl]-2-imidazoline.

Its synthesis involves: 1. Alkylation of 3-(4-methylanilino)phenol. 2. Reaction with 2-chloromethylimidazoline.

Patent and Research

• K. Miescher, A. Marxer, E. Urech, U.S. patent 2,503,059 (1950).
• E. Urech, A. Marxer, K. Miescher, Helv. Chim. Acta, 33, 1386 (1950).

Pharmacokinetics

• Absorption: Rapid onset (IV: ~2 minutes)
• Half-life: ~19 minutes
• Metabolism: Liver (hepatic enzymatic degradation)
• Excretion: Primarily in urine

Adverse Effects

Common side effects include:

• Hypotension (low blood pressure)
• Reflex tachycardia
• Dizziness, flushing
• Nasal congestion (due to vasodilation)

Serious adverse effects:

• Severe hypotension
• Arrhythmias
• Myocardial ischemia (rare)

Contraindications

Phentolamine should not be used in:

• Myocardial infarction (increases cardiac workload)
• Coronary artery disease
• Severe hypotension
• Hypersensitivity to phentolamine

Drug Interactions

• Beta-blockers – Risk of unopposed α-adrenergic effects.
• Vasodilators (e.g., nitroglycerin, hydralazine) – Additive hypotensive effect.
• Sympathomimetics (e.g., epinephrine) – Can lead to unpredictable blood pressure responses.

See Also

• Adrenergic antagonist
• Pheochromocytoma
• Erectile dysfunction
• Vasodilators

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