63-92-3 Usage
Description
Phenoxybenzamine hydrochloride, also known as dibenzyline, is an orally effective, long-acting non-selective alpha-adrenoceptor blocking agent. It is characterized by its ability to block both alpha1 and alpha2 receptors, leading to increased blood flow to the skin, mucosa, and abdominal viscera, as well as a reduction in both supine and erect blood pressures. Notably, it does not affect the parasympathetic system and is used for its "chemical sympathectomy" properties.
Used in Pharmaceutical Industry:
Phenoxybenzamine hydrochloride is used as an antihypertensive agent for the control of episodes of hypertension associated with pheochromocytoma, a condition characterized by the overproduction of epinephrine and a significant elevation of blood pressure.
Used in Endocrine Treatment:
Phenoxybenzamine hydrochloride is utilized in treating pheochromocytoma, a tumor of the medullary layer of the adrenal glands, where its alpha-blocking properties help manage the hypertension and associated symptoms.
Used in Cardiovascular Management:
The drug is employed to control episodes of hypertension and sweating, offering a relatively slow onset and prolonged effect compared to other alpha-blockers. In cases where tachycardia is excessive, phenoxybenzamine may be used in conjunction with a beta-blocker for optimal cardiovascular management.
Used in Urological Treatment:
Phenoxybenzamine hydrochloride has been tested for its efficacy in addressing micturition disorders, such as neurogenic bladder, functional outlet obstruction, and partial prostatic obstruction, leveraging its ability to relax smooth muscles and improve urine flow.
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.
Check Digit Verification of cas no
The CAS Registry Mumber 63-92-3 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 6 and 3 respectively; the second part has 2 digits, 9 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 63-92:
(4*6)+(3*3)+(2*9)+(1*2)=53
53 % 10 = 3
So 63-92-3 is a valid CAS Registry Number.
InChI:InChI=1/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/p+1
63-92-3Relevant articles and documents
A PROCESS FOR THE PREPARATION OF PHENOXYBENZAMINE
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Page/Page column 10; 12, (2018/08/03)
The present invention provides a process for the preparation of N-phenoxyisopropyl ethanolamine of Formula (II) and its conversion to Phenoxybenzamine of Formula (I) or pharmaceutically acceptable salts thereof.
