Phenoxybenzamine

Phenoxybenzamine

Systematic (IUPAC) name
(RS)-N-benzyl-N-(2-chloroethyl)-1-phenoxypropan-2-amine
Clinical data
Trade names	Dibenzyline
AHFS/Drugs.com	monograph
MedlinePlus	a682059
Pregnancy cat.	C (U.S.)
Legal status	?
Routes	Oral
Pharmacokinetic data
Half-life	24 hours
Identifiers
CAS number	59-96-1
ATC code	C04AX02
PubChem	CID 4768
DrugBank	APRD00651
ChemSpider	4604 Y
UNII	0TTZ664R7Z Y
KEGG	D08358 Y
ChEMBL	CHEMBL753 Y
Chemical data
Formula	C18H22ClNO
Mol. mass	303.826 g/mol
SMILES	eMolecules & PubChem
InChI 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 Y Key:QZVCTJOXCFMACW-UHFFFAOYSA-N Y
Y(what is this?)  (verify)

Phenoxybenzamine (marketed under the trade name Dibenzyline) is a non-selective, 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,^[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 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.^[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]

Chemistry

Phenoxybenzamine, N-(2-chloroethyl)-N-(1-methyl-2-phenoxyethyl)benzylamine, is synthesized by reacting phenol with propylenoxide, which forms 1-phenoxy-2-propanol, the chlorination of which with thionyl chloride gives 1-phenoxy-2-propylchloride. Reacting this with 2-aminoethanol leads to formation of 1-phenoxy-2-(2-hydroxyethyl)aminopropane. Alkylation of the secondary amino group gives N-(2-hydroxyethyl)-N-(1-methyl-2-phenoxyethyl)benzylamine, the hydroxyl group of which is chlorinated using thionyl chloride, giving phenoxybenzamine

• J.F. Kerwin, G.E. Ullyot, U.S. Patent 2,599,000 (1952).

Pharmacology

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.

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.^[7]

References

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. doi:10.1111/j.1464-410X.1978.tb06210.x. PMID 88984. 
2. ^ Guzzetta NA (August 2007). "Phenoxybenzamine in the treatment of hypoplastic left heart syndrome: a core review". Anesth. Analg. 105 (2): 312–5. doi:10.1213/01.ane.0000275185.44796.92. PMID 17646482. http://www.anesthesia-analgesia.org/cgi/pmidlookup?view=long&pmid=17646482. 
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. doi:10.1172/JCI33873. PMC 2276786. PMID 18382745. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2276786. 
4. ^ Kjaergaard N, Kjaergaard B, Lauritsen JG (June 1988). "Prazosin, an adrenergic blocking agent inadequate as male contraceptive pill". Contraception 37 (6): 621–9. doi:10.1016/0010-7824(88)90008-X. PMID 2899490. 
5. ^ Homonnai ZT, Shilon M, Paz GF (May 1984). "Phenoxybenzamine—an effective male contraceptive pill". Contraception 29 (5): 479–91. doi:10.1016/0010-7824(84)90022-2. PMID 6430643. 
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. doi:10.1074/jbc.M104167200. PMID 11395517. 
7. ^ Katzung, Trevor et al. Pharmacology Board Review. p.153. Mcgraw Hill, 2007.

This drug article relating to the cardiovascular system is a stub. You can help Wikipedia by expanding it.v · Categories: Alpha blockers IARC Group 2B carcinogens Phenol ethers Organochlorides Cardiovascular system drug stubs Wikimedia Foundation. 2010. Игры ⚽ Поможем написать курсовую Potomac Highlands of West Virginia Montluel Look at other dictionaries: phenoxybenzamine — /fi nok see ben zeuh meen /, n. Pharm. an alpha blocker, C18H22ClNO, used to dilate vascular peripheral blood vessels in the treatment of Raynaud s disease and in pheochromocytoma. [PHEN + OXY 2 + BENZAMINE] * * * …   Universalium phenoxybenzamine — noun an alpha blocker and vasodilator …   Wiktionary phenoxybenzamine — phe·noxy·ben·za·mine ben zə .mēn n a drug that blocks the activity of alpha receptors and is used in the form of its hydrochloride C18H22ClNO·HCl esp. in the treatment of hypertension and sweating due to pheochromocytoma * * * n. a drug that… …   Medical dictionary phenoxybenzamine — phe·noxy·ben·za·mine …   English syllables phenoxybenzamine — n. a drug that dilates blood vessels (see alpha blocker). It is used to reduce high blood pressure in patients with phaeochromocytoma. It is administered by mouth or injection and may cause dizziness and fast heartbeat. Trade names: Dibenyline …   The new mediacal dictionary phenoxybenzamine — fə̇¦näksē¦benzəˌmēn noun Etymology: International Scientific Vocabulary phen + oxy (II) + benz + amine : a drug C18H22ClNO that blocks the activity of alpha receptors and is used in the form of its hydrochloride especially to produce peripheral… …   Useful english dictionary phenoxybenzamine hydrochloride — A potent nonselective adrenergic (α receptor) blocking agent of the β haloalkylamines; blocks the excitatory response of smooth muscle and exocrine glands to epinephrine; used in the treatment of peripheral …   Medical dictionary Norepinephrine — Norepinephrine[1] …   Wikipedia Phentolamine — Systematic (IUPAC) name …   Wikipedia Tolazoline — Systematic (IUPAC) name 2 benzyl 4,5 dihydro 1H imidazole Clinical data AHFS/Drugs.com …   Wikipedia 18+ © Academic, 2000-2024 Contact us: Technical Support, Advertising Dictionaries export, created on PHP, Joomla, Drupal, WordPress, MODx. Mark and share Search through all dictionaries Translate… Search Internet Share the article and excerpts Direct link … Do a right-click on the link above and select “Copy Link”