Systematic (IUPAC) name
Clinical data
Trade names Dibenzyline
Routes of
Pharmacokinetic data
Biological half-life 24 hours
CAS Registry Number  Y
ATC code C04
PubChem CID:
DrugBank  Y
ChemSpider  Y
Chemical data
Formula C18H22ClNO
Molecular mass 303.826 g/mol

Phenoxybenzamine (marketed under the trade name Dibenzyline) is a non-selective, irreversible alpha blocker.


  • Uses 1
    • Investigational 1.1
  • Pharmacology 2
  • See also 3
  • References 4


It is used in the treatment of hypertension, and specifically that caused by pheochromocytoma. It has a slower onset and a longer lasting effect compared with other alpha blockers.

It was also the first alpha blocker to be used for treatment of benign prostatic hyperplasia,[1] although it is currently seldom used for that indication due to unfavourable side effects.

It has been used in the treatment of hypoplastic left heart syndrome.[2]

It is also used in complex regional pain syndrome type 1 due to its anti-adrenergic affects. It has shown to be beneficial if used in the first 3 months of the CRPS diagnosis.


Phenoxybenzamine has long been known to block vas deferens.[3][4][5] As of 2008, research was underway to identify possible drug candidates that share this effect but act specifically on the reproductive tract, unlike phenoxybenzamine.[3]


Phenoxybenzamine is used as an anti-hypertensive due to its efficacy in reducing the vasoconstriction caused by epinephrine (adrenaline) and norepinephrine. Phenoxybenzamine forms a permanent covalent bond with adrenergic receptors. Based on known information about the structures of these receptors, it likely involves attack by the cysteine at position 3.36 in transmembrane helix 3 to form a stable linkage.[6] Thus, it remains permanently bound to the receptor, preventing adrenaline and noradrenaline from binding. This causes vasodilatation in blood vessels, due to its antagonistic effect at the alpha-1 adrenoceptor found in the walls of blood vessels, resulting in a drop in blood pressure. A side effect of phenoxybenzamine is reflex tachycardia.

As a non-selective alpha receptor antagonist, it will also affect both the postsynaptic alpha 1 and presynaptic alpha 2 receptors in the nervous system, and so reduce sympathetic activity. This results in further vasodilation, pupil constriction, an increase in GI tract motility and secretions, and glycogen synthesis.

Clinically, non-selective alpha antagonists block alpha receptors (but do not differentiate between alpha-1 and alpha-2). They are used as antihypertensives because they block alpha-receptor-mediated vasoconstriction. The block on alpha-2 receptors further potentiates beta-effects, increasing cardiac output.

Phenoxybenzamine has a long-lasting action, binding covalently to the alpha receptors. Its only current clinical use is in preparing patients with phaeochromocytoma for surgery; its irreversible antagonism and the resultant depression in the maximum of the agonist dose-response curve are desirable in a situation where surgical manipulation of the tumour may release a large bolus of pressor amine into the circulation. Typically, phenoxybenzamine is not used in the long term, as new receptors are made to upregulate alpha stimulation. The main limiting side-effects of alpha antagonists is that the baroreceptor reflex is disrupted and thus this can cause postural hypotension.

Phenoxybenzamine also has irreversible antagonist/weak partial agonist properties at the serotonin 5-HT2A reecptor.[7][8][9][10] Due to its 5-HT2A receptor antagonism, phenoxybenzamine is useful in the treatment of carcinoid tumor, a neoplasm that secretes large amounts of serotonin and causes diarrhea, bronchoconstriction, and flushing.[8]

See also


  1. ^ Caine M, Perlberg S, Meretyk S (1978). "A placebo-controlled double-blind study of the effect of phenoxybenzamine in benign prostatic obstruction". British journal of urology 50 (7): 551–4.  
  2. ^ Guzzetta NA (August 2007). "Phenoxybenzamine in the treatment of hypoplastic left heart syndrome: a core review". Anesth. Analg. 105 (2): 312–5.  
  3. ^ a b Aitken RJ, Baker MA, Doncel GF, Matzuk MM, Mauck CK, Harper MJ (April 2008). "As the world grows: contraception in the 21st century". J Clin Invest 118 (4): 1330–43.  
  4. ^ Kjaergaard N, Kjaergaard B, Lauritsen JG (June 1988). "Prazosin, an adrenergic blocking agent inadequate as male contraceptive pill". Contraception 37 (6): 621–9.  
  5. ^ Homonnai ZT, Shilon M, Paz GF (May 1984). "Phenoxybenzamine—an effective male contraceptive pill". Contraception 29 (5): 479–91.  
  6. ^ Frang H, Cockcroft V, Karskela T, Scheinin M, Marjamäki A (2001). "Phenoxybenzamine binding reveals the helical orientation of the third transmembrane domain of adrenergic receptors". J. Biol. Chem. 276 (33): 31279–84.  
  7. ^ Doggrell, S. A. (1995). "Increase in affinity and loss of 5-hydroxytryptamine2A-receptor reserve for 5-hydroxytryptamine on the aorta of spontaneously hypertensive rats". Journal of Autonomic Pharmacology 15 (5): 371–377.  
  8. ^ a b Anthony Trevor; Bertram Katzung; Susan Masters (2008). Katzung & Trevor's Pharmacology Examination and Board Review: Eighth Edition. McGraw Hill Professional. pp. 153,500.  
  9. ^ B. Olivier; I. van Wijngaarden; W. Soudijn (10 July 1997). Serotonin Receptors and their Ligands. Elsevier. pp. 206–.  
  10. ^ Timothy S. Gaginella; James J. Galligan (25 July 1995). Serotonin and Gastrointestinal Function. CRC Press. pp. 56–.