|Drug class||Alpha blocker|
|Main uses||Pheochromocytoma, peripheral vascular disease, urinary retention|
|Side effects||Stuffy nose, small pupils, low blood pressure with standing|
|Elimination half-life||24 hours|
|Chemical and physical data|
|Molar mass||303.83 g·mol−1|
|3D model (JSmol)|
Phenoxybenzamine, sold under the brand name Dibenzyline among others, is a medication used to manage pheochromocytoma, peripheral vascular disease, and urinary retention. It is taken by mouth. Effects begin in hours and can last for a week.
Common side effects include a stuffy nose, small pupils, and low blood pressure with standing. Other side effects may include heart problems as a result of a faster heart rate. It should not be used in people with porphyrias. It is an alpha blocker.
Phenoxybenzamine was approved for medical use in the United States in 1953. It is available as a generic medication. In the United States 60 tablets of 10 mg costs about 1,800 USD as of 2021. In the United Kingdom this amount costs the NHS about £240.
It is also used in complex regional pain syndrome (CRPS) type 1 due to its anti-adrenergic effects. It has shown to be beneficial if used in the first 3 months of the CRPS diagnosis.
It is started at a dose of 10 mg twice per day and may be increased up to 40 mg three times per day.
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. Thus, it remains permanently bound to the receptor, preventing adrenaline and noradrenaline from binding. This causes vasodilation 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 pheochromocytoma 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 receptor. 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.
|Enantiomers of phenoxybenzamine|
CAS number: 71799-91-2
CAS number: 71799-90-1
Phenoxybenzamine has long been known to block ejaculation without affecting semen quality or ability to achieve orgasm, which could make it an effective male contraceptive. This effect is completely reversible, and is believed to be the result of alpha-1 adrenoceptor blockade in the longitudinal muscles of the vas deferens.
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