Phenoxybenzamine

Structural formula
	1: 1 mixture of ( R ) - and ( S ) -form
General
Non-proprietary name	Phenoxybenzamine
other names	( RS ) - N -Benzyl- N - (2-chloroethyl) -1- (phenoxy) -2-aminopropane ( IUPAC ); (±) - N -Benzyl- N - (2-chloroethyl) -1- (phenoxy) -2-aminopropane; ( RS ) -Benzyl- (2-chloroethyl) - (β-phenoxyisopropyl) amine; (±) -Benzyl- (2-chloroethyl) - (β-phenoxyisopropyl) amine; Dibenzyline;
Molecular formula	C 18 H 22 ClNO
External identifiers / databases
EC number	200-446-8
ECHA InfoCard	100,000,406
PubChem	4768
ChemSpider	4604
DrugBank	DB00925
Wikidata	Q419824
Drug information
ATC code	C04 AX02 , G04 BD20
Drug class	Alpha blockers
properties
Molar mass	303.83 g mol −1
Physical state	firmly
Melting point	38-40 ° C ; 137.5–140 ° C (hydrochloride)
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
H and P phrases	H: 302-351
	P: 281
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Phenoxybenzamine is a drug that belongs to the group of alpha blockers (α-sympatholytics). It has a peripheral vasodilator effect and is used as an antihypertensive agent in pheochromocytoma .

In Germany, phenoxybenzamine is also used as a urological spasmolytic for neurogenic bladder voiding disorders. The active ingredient is also used in cats to improve bladder emptying in obstructive Feline Lower Urinary Tract Disease .

The active ingredient is used in racemic form as the hydrochloride .

Mechanism of action

Phenoxybenzamine is an irreversible blocker of α ₁ - and α ₂ -receptors , whereby the blockade is based on an alkylation of the receptor .

unwanted effects

The most serious side effect of phenoxybenzamine is orthostatic hypotension , which is characteristic of alpha blockers. In animal experiments, the active ingredient has been shown to be carcinogenic when administered intraperitoneally .

Manufacturing

The synthesis of racemic phenoxybenzamine succeeds step by step starting from 1-phenoxypropan-2-ol . First, the is alcohol function by means of thionyl chloride by a chlorine atom substituted , then a nucleophilic substitution with ethanolamine . The secondary amine obtained in this way is reacted with benzyl chloride and then the alcohol function introduced with the ethanolamine is reacted analogously to the first step by thionyl chloride to form the chlorine derivative . This is initially obtained as the hydrochloride , from which the free base is released with sodium hydroxide solution . The 1-phenoxypropan-2-ol required as a starting material can be obtained from the common industrial products propylene oxide and phenol .

Stereoisomerism

Phenoxybenzamine contains a stereocenter, so there are two enantiomers , the ( R ) form and the ( S ) form. All commercial preparations contain the drug as a racemate .

Enantiomers of phenoxybenzamine
CAS number: 71799-91-2	CAS number: 71799-90-1

Trade names

Phenoxybenzamine is commercially available in Germany and Austria under the name Dibenzyran . In the United States, the trade name is Dibenzyline .

literature

T. Karow (Ed.): Pharmacology and Toxicology. Cologne 2005, p. 68.
CJ Estler (Ed.): Pharmacology and Toxicology. 4th edition. Schattauer, Stuttgart a. New York 1995, pp. 69-71.
H. Hildebrandt (Ed.): Pschyrembel Clinical Dictionary. 257th edition. Walter de Gruyter, Berlin / New York 1994.

Individual evidence

↑ ^a ^b Patent US2983719 : Published 1954 , Inventors: JF Kerwin, GE Ullyot. ‌
↑ ^a ^b ^c Entry on phenoxybenzamine. In: Römpp Online . Georg Thieme Verlag, accessed on July 23, 2019.
↑ ^a ^b Datasheet Phenoxybenzamine hydrochloride from Sigma-Aldrich , accessed on April 18, 2011 ( PDF ).
↑ merckvetmanual
^ AR Sexton, EC Britton: Synthesis and identification of propylene glycol phenyl ethers. In: J. Am. Chem. Soc. 70, 1948, pp. 3606-3607.
↑ F. v. Bruchhausen, G. Dannhardt, S. Ebel, AW Frahm, E. Hackenthal, U. Holzgrabe (Eds.): Hagers Handbook of Pharmaceutical Practice: Volume 9: Material PZ , Springer Verlag, Berlin, Edition 5, 2014, p. 140, ISBN 978-3-642-63389-8 .

[Kerwin-1] Patent US2983719 : Published 1954 , Inventors: JF Kerwin, GE Ullyot. ‌

[römpp-2] Entry on phenoxybenzamine. In: Römpp Online . Georg Thieme Verlag, accessed on July 23, 2019.

[Sigma-3] Datasheet Phenoxybenzamine hydrochloride from Sigma-Aldrich , accessed on April 18, 2011 ( PDF ).

[4] rckvetmanual

[Sexton-5] AR Sexton, EC Britton: Synthesis and identification of propylene glycol phenyl ethers. In: J. Am. Chem. Soc. 70, 1948, pp. 3606-3607.

[Hager-6] F. v. Bruchhausen, G. Dannhardt, S. Ebel, AW Frahm, E. Hackenthal, U. Holzgrabe (Eds.): Hagers Handbook of Pharmaceutical Practice: Volume 9: Material PZ , Springer Verlag, Berlin, Edition 5, 2014, p. 140, ISBN 978-3-642-63389-8 .