Phenoxybenzamine hydrochloride Chemical Properties

Melting point:

137.5°C

storage temp. 

15-25°C

solubility 

soluble in organic solvents such as ethanol, DMSO, and dimethyl formamide (DMF).

pka

pKa 4.4 (Uncertain)

form 

powder

color 

white

Water Solubility 

<0.01 g/100 mL at 18.5 ºC

Merck 

14,7256

Stability:

Stable for 2 years as supplied. Solutions in DMSO or distilled water may be stored at -20°C for up to 3 months.

CAS DataBase Reference

63-92-3(CAS DataBase Reference)

IARC

2B (Vol. 24, Sup 7) 1987

EPA Substance Registry System

N-(2-Chloroethyl)-N-(1-methyl-2-phenoxyethyl)benzylamine hydrochloride (63-92-3)

Safety Information

Hazard Codes 

Xn

Risk Statements 

22-40

Safety Statements 

22-36/37/39-45

WGK Germany 

3

RTECS 

DP3750000

HS Code 

2922299000

MSDS

• Language:English Provider:2-(N-Benzyl-2-chloroethylamino)-1-phenoxypropane hydrochloride
• Language:English Provider:SigmaAldrich

Phenoxybenzamine hydrochloride Usage And Synthesis

Description

Phenoxybenzamine hydrochloride (dibenzyline) is an orally effective, long-acting non-selective (alpha1 and alpha2) alpha-adrenoceptor blocking agent. It is used for the control of episodes of hypertension associated withpheochromocytoma. It literally produces a "chemical sympathectomy". It increases blood flow to the skin, mucosa and abdominal viscera, and lowers both supine and erect blood pressures. It has no effect on the parasympathetic system. The initialdose is 10 mg/day, increased by 10 mg every 4 days till the desired response is attained.The usual dosage range is 20-60mg/day.

Chemical Properties

white crystalline solid or powder. Odorless. soluble in ethanol, chloroform, propylene glycol, slightly soluble in benzene, slightly soluble in cold water. The melting point of its free base is 38-40 ° C, and it is soluble in benzene.

Originator

Dibenzyline, SKF, US ,1953

Uses

Phenoxybenzamine is used in treating pheochromocytoma, swelling of the medullary layer of the adrenal glands, during which a large quantity of epinephrine is produced, which leads to a significant elevation of blood pressure.

Uses

Phenoxybenzamine (5.0 to 60.0 mg/day) is used in order to control episodes of hypertension and sweating, it has a relatively slow onset and prolonged effect when compared to alternative α-blockers. If tachycardia is excessive, it may also be necessary to use a betablocker concomitantly. In addition, phenoxybenzamine has been tested for its efficacy in micturition disorders resulting from neurogenic bladder, functional outlet obstruction, and partial prostatic obstruction.

Definition

ChEBI: Phenoxybenzamine hydrochloride is an organic molecular entity.

brand name

Dibenzyline (WellSpring).

General Description

Phenoxybenzamine hydrochloride is a white crystalline powder. Melting point 137.5-140°C. Used as an antihypertensive drug.

Air & Water Reactions

Light sensitive and may be sensitive to exposure to air . Insoluble in water.

Mechanism of action

Phenoxybenzamine hydrochloride is a noncompetitive alpha-adrenergicreceptor blocker, and its action cannot be nullified by increasing the amount of agonist, or agonists. It causes epinephrine reversal in that the administration of epinephrine after pretreatment with phenoxybenzamine elicits vasodilation, and, conversely, phenoxybenzamine reverses epinephrine-mediated vasoconstriction to vasodilation. It may inhibit neuronal and extraneuronal uptake mechanisms of norepinephrine. At higher concentrations, it inhibits responses to 5-HT, histamine and acetylcholine.

Clinical Use

Oral phenoxybenzamine is used for the preoperativemanagement of patients with pheochromocytoma and in thechronic management of patients whose tumors are notamenable to surgery. Only about 20% to 30% of an oraldose is absorbed.

Side effects

The adverse effects of phenoxybenzamine include nasal congestion, miosis, postural hypotension, tachycardia, and inhibition of ejaculation.

Safety Profile

Confumed carcinogen with experimental carcinogenic and teratogenic data. Poison by intraperitoneal,intravenous, and subcutaneous routes. Human systemic effects by ingestion: changes in tubules, including acute renal failure, acute tubular necrosis. Moderately toxic by ingestion. Other experimental reproductive effects. Mutation data reported. A long-acting adrenergic blocker. When heated to decomposition it emits very toxic fumes of NOx and Cl-.

Synthesis

Phenoxybenzamine, N-(2-chloroethyl)-N-(1-methyl-2-phenoxyethyl) benzylamine (12.2.5), is synthesized by reacting phenol with propylenoxide, which forms 1-phenoxy-2-propanol (12.2.1), the chlorination of which with thionyl chloride gives 1-phenoxy-2-propylchloride (12.2.2). Reacting this with 2-aminoethanol leads to formation of 1-phenoxy-2-(2-hydroxyethyl)aminopropane (12.2.3). Alkylation of the secondary amino group gives N-(2-hydroxyethyl)-N-(1-methyl-2-phenoxyethyl)benzylamine (12.2.4), the hydroxyl group of which is chlorinated using thionyl chloride, giving phenoxybenzamine (12.2.5) [31].

Veterinary Drugs and Treatments

Phenoxybenzamine is used in small animals primarily for its effect in reducing internal urethral sphincter tone in dogs and cats when urethral sphincter hypertonus is present. It can also be used to treat the hypertension associated with pheochromocytoma prior to surgery or as adjunctive therapy in endotoxicosis.
In horses, phenoxybenzamine has been used for preventing or treating laminitis in its early stages and to treat secretory diarrheas.

Drug interactions

Dibenzyline (phenoxybenzamine hydrochloride) may interact with compounds that stimulate both alpha- and beta-adrenergic receptors (i.e., epinephrine) to produce an exaggerated hypotensive response and tachycardia.

Carcinogenicity

Phenoxybenzamine hydrochloride is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals.

Metabolism

Metabolised in the liver and excreted in the urine and bile, but small amounts remain in the body for several days.

Dosage

Initially, 10 mg of Dibenzyline (phenoxybenzamine hydrochloride) twice a day. Dosage should be increased every other day, usually to 20 to 40 mg 2 or 3 times a day, until an optimal dosage is obtained, as judged by blood pressure control.

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