Phenoxybenzamine

Phenoxybenzamine

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Systematic (IUPAC) name
(RS)-N-benzyl-N-(2-chloroethyl)-1- phenoxy-propan-2-amine
Clinical data
Pregnancy category	C (U.S.)
Routes of administration	Oral
Pharmacokinetic data
Biological half-life	24 hours
Identifiers
CAS Number	59-96-1
ATC code	C04AX02 (WHO)
PubChem	CID 4768
DrugBank	APRD00651
Chemical data
Formula	C18H22ClNO
Molar mass	303.826 g/mol[[]]
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Phenoxybenzamine (marketed under the trade name Dibenzyline) is a non-specific, irreversible alpha antagonist.

Uses

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, 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.

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 CRPS diagnosis.

It is currently under investigation for use as a male contraceptive. Phenoxybenzamine has been found to block ejaculation, which not only gives it the potential to be an effective contraceptive, but could also lead to much cleaner sex in that it would hinder the release of semen-borne pathogens. Studies have found that the quality of the semen is unaffected and the results are reversible by simply discontinuing the treatment.

Pharmacology

Phenoxybenzamine is used as an anti-hypertensive due to its efficacy in reducing the vasoconstriction caused by adrenaline and noradrenaline. Phenoxybenzamine forms a permanent covalent bond with adrenergic receptors. Based on what we know 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 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.

It will also affect the postsynaptic alpha 1 and 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.

It also has partial agonist/antagonist properties at the serotonin 5-HT2A receptor. Due to its 5-HT2A antagonism, it is useful in the treatment of carcinoid tumor, a neoplasm that secretes large amounts of serotonin and causes diarrhea, bronchoconstriction, and flushing.

References

de:Phenoxybenzamin pt:Fenoxibenzamina