Phenoxybenzamine

Source: Wikipedia, the free encyclopedia.
Phenoxybenzamine
Clinical data
Trade namesDibenzyline
AHFS/Drugs.comMonograph
MedlinePlusa682059
Pregnancy
category
  • AU: B2
Routes of
administration		Oral
ATC code
Pharmacokinetic data
Elimination half-life24 hours
Identifiers
  • (RS)-N-Benzyl-N-(2-chloroethyl)-1-phenoxypropan-2-amine
JSmol)
ChiralityRacemic mixture
  • ClCCN(C(COc1ccccc1)C)Cc2ccccc2
  • InChI=1S/C18H22ClNO/c1-16(15-21-18-10-6-3-7-11-18)20(13-12-19)14-17-8-4-2-5-9-17/h2-11,16H,12-15H2,1H3 checkY
  • Key:QZVCTJOXCFMACW-UHFFFAOYSA-N checkY
  (verify)

Phenoxybenzamine (PBZ,[1] marketed under the trade names Dibenzyline and Dibenyline) is a non-selective, irreversible alpha blocker.

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,[2] 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.[3]

It is also used in

antiadrenergic
effects. It has shown to be beneficial if used in the first 3 months of the CRPS diagnosis.

Investigational

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.[4][5][6] A dose of 20 mg/day results in aspermia due to reversible paralyzing effects on the vas deferens, ampulla, and ejaculatory ducts.[7] Due to these actions, phenoxybenzamine is also useful for the treatment of premature ejaculation in men.[7]

Pharmacology

Phenoxybenzamine is used as an anti-hypertensive due to its efficacy in reducing the

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.[8] 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

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

carcinoid tumor, a neoplasm that secretes large amounts of serotonin and causes diarrhea, bronchoconstriction, and flushing.[10]

Stereoisomerism

Phenoxybenzamine contains a stereocenter, so there are two

racemate.[13]

Enantiomers of phenoxybenzamine

(R)-Phenoxybenzamine
CAS number: 71799-91-2
(S)-Phenoxybenzamine
CAS number: 71799-90-1

See also

References

  1. ^ Bradley K. "Clinical Guideline: Phaeochromocytoma Diagnosis and Management" (PDF). University Hospitals Bristol. NHS Foundation Trust. Archived from the original (PDF) on 25 March 2023.
  2. PMID 88984
    .
  3. PMID 17646482
    .
  4. PMID 18382745
    .
  5. PMID 2899490
    .
  6. PMID 6430643
    .
  7. ^
    ISBN 978-981-10-3694-1
    .
  8. PMID 11395517
    .
  9. PMID 8744977
    .
  10. ^
    ISBN 978-0-07-148869-3
    .
  11. ISBN 978-0-08-054111-2
    .
  12. ISBN 978-0-8493-8387-8
    .
  13. ISBN 978-3-642-63389-8
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Phenoxybenzamine&oldid=1182204628"