(±)-Phenoxybenzamine

185.22184

303.83

200-446-8

DTXSID0023458

CRYSTALS FROM PETROLEUM ETHER

C - Cardiovascular system

2922299090

12.5

4.7

Solid

1.102g/cm3

38-40 °C

381.5ºC at 760mmHg

184.5ºC

1.559

1.03e-02 g/L

LD50 oral in rat: 2500mg/kg

Odorless /Phenoxybenzamine hydrochloride/|Almost tasteless /Phenoxybenzamine hydrochloride/|Lambda max (in chloroform) 272 nm, A(1%, 1cm) = 56.3; 279 nm, A(1%, 1cm) = 46.1 /Phenoxybenzamine hydrochloride/|SOLN IN 50: 50 ETHANOL:PROPYLENE GLYCOL ARE STABLE WHEN STORED BELOW 25 °C /PHENOXYBENZAMINE HYDROCHLORIDE/|NEUTRAL & ALKALINE SOLN ARE UNSTABLE; SENSITIVE TO OXIDATION & PHOTODEGRADATION /PHENOXYBENZAMINE HYDROCHLORIDE/

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

BENFEY BG; TWO LONG ACTING ALPHA-ADRENOCEPTOR BLOCKING DRUGS: BENEXTRAMINE AND PHENOXYBENZAMINE. TRENDS PHARMACOL SCI 3 (12): 470 (1982). A REVIEW ON PHARMACOLOGY OF BENEXTRAMINE & PHENOXYBENZAMINE.|Bioassay of Phenoxybenzamine Hydrochloride for Possible Carcinogenicity (1978) Technical Rpt Series No. 72 DHEW Pub No. (NIH) 78-1322, U.S. Department of Health Education and Welfare, National Cancer Institute, Bethesda, MD 20014|National Toxicology Program. Eleventh Report on Carcinogens (2005). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. Phenoxybenzamine Hydrochloride (63-92-3) is listed as reasonably anticipated to be a human carcinogen. /Phenoxybenzamine Hydrochloride/[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s146phen.pdf]

Symptoms of overdose are largely the result of block of the sympathetic nervous system and of the circulating epinephrine. They may include postural hypotension resulting in dizziness or fainting, tachycardia, particularly postural, vomiting; lethargy, and shock.

INHIBITION OF COMPENSATORY VASOCONSTRICTION ALSO EXAGGERATES DEPRESSOR EFFECTS OF OPIOIDS & OTHER AGENTS THAT ACT DIRECTLY TO RELAX VASCULAR SMOOTH MUSCLE.|EXPTL HEMORRHAGIC SHOCK WAS PRODUCED IN 50 DOGS & METABOLIC STATUS WAS ASSESSED. ADRENERGIC BLOCKADE WITH PHENOXYBENZAMINE HAD PROTECTIVE ACTION ON METABOLIC STATUS BUT BLOOD LOSS REQUIRED TO ATTAIN SAME DEGREE OF HYPOTENSION WAS LESS. ADMIN OF PHENOXYBENZAMINE & PROPRANOLOL TOGETHER (COMBINED ADRENERGIC BLOCKADE) GAVE BEST RESULT REGARDING METABOLIC STATUS.|Prior administration of phenoxybenzamine may decrease the pressor response to phenylephrine.|Prior administration of phenoxybenzamine may block the pressor response to methoxamine, possibly resulting in severe hypotension.|For more Interactions (Complete) data for PHENOXYBENZAMINE (11 total), please visit the HSDB record page.

A bioassay of phenoxybenzamine hydrochloride for possible carcinogenicity was conducted by administering the test chemical by ip injection to Sprague-Dawley rats and B6C3F1 mice. ... Groups of 35 rats of each sex were administered phenoxybenzamine hydrochloride at one of two doses, either 5 or 10 mg/kg body weight, 3 days/wk for 52 wk, then observed for an additional 31 or 32 wk. The vehicle used for most of the period of the bioassay was 6% propylene glycol in saline, although other vehicles, including 0.05% polysorbate 80 in saline, were used at the beginning. Controls consisted of groups of 10 vehicle controls and 10 untreated controls of each sex. All surviving rats were killed at 83-85 wk. Groups of 35 mice of each sex were administered phenoxybenzamine hydrochloride at two doses, either 12.5 or 25 mg/kg body weight 3 days/wk for 50 or 52 wk, then observed for an additional 31-33 wk. Controls consisted of groups of 15 males and 15 females which were administered the vehicle (vehicle controls), and groups of 14 males and 16 females which were untreated (untreated controls). All surviving mice were killed at 83-85 wk. ... Under the conditions of this bioassay, phenoxybenzamine hydrochloride was carcinogenic (sarcomagenic) for the peritoneum of both sexes of Sprague-Dawley rats and B6C3F1 mice.

For the treatment of phaeochromocytoma (malignant), benign prostatic hypertrophy and malignant essential hypertension.

Adrenergic alpha-Antagonists; Antihypertensive Agents; Sympatholytics; Vasodilator Agents|FORMER USE: PREOPERATIVE ADMIN ... /OF ADRENERGIC BLOCKING AGENT, PHENOXYBENZAMINE/ SHOWN TO IMPROVE POSTOPERATIVE CARDIOVASCULAR & RENAL FUNCTION FOLLOWING EXTENDED PERIODS OF EXTRACORPOREAL CIRCULATION ASSOC WITH CARDIAC SURGERY. ... ALSO ... USED TO REDUCE RENAL VASOSPASM & TO IMPROVE PERFUSION, PARTICULARLY OF OUTER CORTEX, DURING SHORT-TERM PRESERVATION OF ... KIDNEYS FOR TRANSPLANTATION. PHENOXYBENZAMINE MAY INCR VIABILITY OF RENAL & HEPATIC CELLS SUBJECTED TO PERIODS OF INTERRUPTED BLOOD FLOW TO THESE ORGANS, & DRUG HAS BEEN SHOWN TO IMPROVE SURVIVAL OF EXPERIMENTAL SKIN FLAPS.|Phenoxybenzamine is indicated to control episodes of hypertension and sweating in the treatment of pheochromocytoma as preoperative preparation for surgery, in management of patients when surgery is contraindicated, and in chronic management of patients with malignant pheochromocytoma.|PHENOXYBENZAMINE ... OBSERVED TO RELIEVE VASOSPASM & REDUCE SENSITIVITY TO COLD IN RAYNAUD'S SYNDROME. ... HIGH SPINAL CORD TRANSECTION COMMONLY LEADS TO AUTONOMIC HYPERREFLEXIA WITH PAROXYSMAL ELEVATIONS IN BLOOD PRESSURE FROM BOTH CUTANEOUS & VISCERAL STIMULI, PARTICULARLY THOSE FROM THE URINARY BLADDER. IT HAS BEEN REPORTED THAT THESE PRESSOR EPISODES & THE ASSOC SIGNS & SYMPTOMS CAN BE WELL CONTROLLED BY ... PHENOXYBENZAMINE. ALPHA-ADRENERGIC BLOCKADE HAS BEEN SHOWN TO BE BENEFICIAL IN HEART FAILURE WITH PULMONARY EDEMA & IN ACUTE MYOCARDIAL INFARCTION WHERE PAIN CAN ACCENTUATE THE VASOCONSTRICTION.|For more Therapeutic Uses (Complete) data for PHENOXYBENZAMINE (14 total), please visit the HSDB record page.

BECAUSE OF DANGER OF SEVERE HYPOTENSION WHEN DRUG IS ADMIN IN PRESENCE OF HYPOVOLEMIA, IV ADMIN MUST BE SLOW, PATIENT MUST BE KEPT UNDER CONSTANT OBSERVATION, & BLOOD OR APPROPRIATE PLASMA-VOL EXPANDER MUST BE ON HAND TO CORRECT ANY DEFICIT REVEALED BY HEMODYNAMIC RESPONSE.|... INJECTION SHOULD BE ONLY IV BECAUSE OF THEIR IRRITANT PROPERTIES. /HALOALKYLAMINE ADRENERGIC BLOCKING AGENTS/|PHENOXYBENZAMINE SHOULD NOT BE GIVEN TO PATIENT WITH COMPENSATED CONGESTIVE HEART FAILURE, & IT SHOULD BE USED CAUTIOUSLY IF THERE IS CEREBRAL OR CORONARY ARTERIOSCLEROSIS OR RENAL INSUFFICIENCY.|PHENOXYBENZAMINE SIDE EFFECTS INCL: MOUTH DRYNESS, NASAL CONGESTION, DROWSINESS & FATIGUE, NAUSEA & VOMITING, PALPITATIONS, EJACULATORY FAILURE, & RETROGRADE EJACULATION. RESULTS OF STUDY SUGGEST THAT EJACULATORY FAILURE WAS DUE TO LACK OF SEMINAL EMISSION INTO POSTERIOR URETHRA, RATHER THAN RETROGRADE EJACULATION. /PHENOXYBENZAMINE HYDROCHLORIDE/

Phenoxybenzamine is indicated for the control of episodes of hypertension and sweating that occur with a disease called pheochromocytoma. If tachycardia is excessive, it may be necessary to use a beta-blocking agent concomitantly. Phenoxybenzamine is a long-acting, adrenergic, alpha-receptor blocking agent which can produce and maintain "chemical sympathectomy" by oral administration. 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. Phenoxybenzamine works by blocking alpha receptors in certain parts of the body. Alpha receptors are present in the muscle that lines the walls of blood vessels. When the receptors are blocked by Phenoxybenzamine, the muscle relaxes and the blood vessels widen. This widening of the blood vessels results in a lowering of blood pressure.

Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma. (See all compounds classified as Adrenergic alpha-Antagonists.)|Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. (See all compounds classified as Antihypertensive Agents.)|Drugs used to cause dilation of the blood vessels. (See all compounds classified as Vasodilator Agents.)

Twenty to 30 percent of orally administered phenoxybenzamine appears to be absorbed in the active form.|PHENOXYBENZAMINE HAS HIGH LIPID SOLUBILITY AT BODY PH, & ACCUMULATION IN FAT MAY OCCUR AFTER LARGE DOSES. ... OVER 50% OF RADIOACTIVITY OF IV ADMIN PHENOXYBENZAMINE IS EXCRETED IN 12 HR & OVER 80% IN 24 HR, BUT SMALL AMT REMAIN IN VARIOUS TISSUES FOR AT LEAST A WK.|Absorption from the gastrointestinal tract is incomplete and variable, and only about 20 to 30% of the drug is absorbed in an active form after oral administration.|PHENOXYBENZAMINE COMBINES IRREVERSIBLY WITH SMOOTH MUSCLE ADRENERGIC EXCITATORY RECEPTORS, THROUGH ALKYLATION, SO THAT COMPLETE BLOCKAGE, ONCE INDUCED, MAY LAST FOR SEVERAL DAYS.|IV INJECTION OF /0.54 MG/ (14)C-PHENOXYBENZAMINE HYDROCHLORIDE IN NMRI MICE REMAINED IN BLOOD FOR 40 MIN. RADIOACTIVE MATERIAL WAS THEREAFTER FOUND IN BROWN FAT, LIVER & KIDNEY; OTHER ORGANS (NOTABLY THE HEART & CNS) ATTAINED RELATIVELY HIGHER ACTIVITY, WHICH PERSISTED FOR 4 DAYS /BILIARY EXCRETION WAS AN IMPORTANT ROUTE OF ELIMINATION/. 4 HR AFTER IV INJECTION OF (14)C-PHENOXYBENZAMINE HYDROCHLORIDE, THE BILE FROM 2 ANESTHETIZED MALE SPRAGUE-DAWLEY RATS CONTAINED 29.3% & 32.8% OF ADMIN RADIOACTIVITY. /PHENOXYBENZAMINE HYDROCHLORIDE/

AFTER ORAL OR IP ADMIN OF (15)N-LABELLED PHENOXYBENZAMINE HYDROCHLORIDE TO RATS (20 MG/KG BODY WT) & AFTER ORAL ADMIN TO DOGS (10 MG/KG BODY WT), THE FOLLOWING URINARY METABOLITES WERE IDENTIFIED: N-BENZYL-N-(PARA-HYDROXYPHENOXYISOPROPYL)AMINE WAS FOUND TO BE THE MAJOR METABOLITE IN BOTH SPECIES; N-BENZYL-N-PHENOXYISOPROPYLAMINE WAS THE MINOR METABOLITE IN DOGS & WAS ALSO OBSERVED IN SMALL AMT IN RATS, ONLY AFTER IP INJECTION; & PHENOXYISOPROPYLAMINE WAS FOUND TO BE A METABOLITE IN DOGS. 2-BENZYLAMINO-1-PROPANOL WAS FOUND IN RAT URINE AFTER IP BUT NOT AFTER ORAL DOSING. /PHENOXYBENZAMINE HYDROCHLORIDE/|N-BENZYL-N-(PARA-HYDROXYPHENOXYISOPROPYL)AMINE WAS IDENTIFIED IN THE URINE OF TWO PT TREATED ORALLY WITH 10 MG/DAY PHENOXYBENZAMINE HYDROCHLORIDE. /PHENOXYBENZAMINE HYDROCHLORIDE/

24 hours|The half-life of phenoxybenzamine is probably less that 24 hours. However, since the drug inactivates alpha-adrenergic receptors irreversibly, the duration of its effect is dependent not only on its presence but also on the rate of synthesis of alpha-adrenergic receptors.

Phenoxybenzamine produces its therapeutic actions by blocking alpha receptors, leading to a muscle relaxation and a widening of the blood vessels. This widening of the blood vessels results in a lowering of blood pressure.|ALPHA-ADRENERGIC BLOCKADE IS DUE TO DIRECT ACTION ON ALPHA-ADRENERGIC RECEPTORS & IS INDEPENDENT OF ANY EFFECTS ON ADRENERGIC NERVES OR ON BASIC RESPONSE MECHANISMS OF EFFECTOR CELLS.|Nonselective alpha-adrenergic blockade; phenoxybenzamine combines irreversibly with post ganglionic alpha-adrenergic receptor sites, preventing or reversing effects of endogenous or exogenous catecholamines; no effect on beta-adrenergic receptors.|PHENOXYBENZAMINE INCR RATE OF TURNOVER OF NOREPINEPHRINE IN THE PERIPHERY, WHICH IS ASSOC WITH INCR TYROSINE HYDROXYLASE ACTIVITY. IN INTACT ANIMALS, THESE EFFECTS ARE PROBABLY PREDOMINANTLY DUE TO INCR SYMPATHETIC NERVE ACTIVITY, A REFLEX RESPONSE TO ALPHA-ADRENERGIC BLOCKADE, SINCE THE EFFECT CAN BE INHIBITED BY GANGLIONIC BLOCKING AGENTS. PHENOXYBENZAMINE ... ALSO INCR THE AMT OF NEUROTRANSMITTER RELEASED BY EACH NERVE IMPULSE. THIS APPEARS TO BE DUE TO BLOCKADE OF PRESYNAPTIC ALPHA2 RECEPTORS, WHICH MEDIATE A NEGATIVE FEEDBACK MECHANISM THAT INHIBITS THE RELEASE OF NOREPINEPHRINE.|WITH INCR DOSES OF BLOCKING AGENT, DOSE-RESPONSE CURVE FOR AGONIST IS SHIFTED PROGRESSIVELY TO RIGHT AS NUMBER OF AVAILABLE RECEPTORS IS REDUCED. WHEN THE NUMBER OF FUNCTIONAL RECEPTORS IS REDUCED TO THE DEGREE THAT THE ORIGINAL MAXIMAL RESPONSE IS NO LONGER ATTAINABLE WITH A FULL AGONIST, THE DOSE-RESPONSE CURVE DOES NOT SHIFT FURTHER TO THE RIGHT; ADDNL RECEPTOR BLOCKADE NOW CAUSES A DEPRESSION OF THE MAXIMAL RESPONSE.|For more Mechanism of Action (Complete) data for PHENOXYBENZAMINE (6 total), please visit the HSDB record page.

Treatment: Stabilization. Establish adequate respiratory function. Normal tidal volume: 10-15 ml/kg. Endotracheal intubation with assisted ventilation may be required. Gut Decontamination. Emesis induction is indicated unless the patient is comatose, is convulsing, or has no gag reflex. If these are present, endotracheal intubation must be performed with a cuffed endotracheal tube before a large-bore gastric tube is inserted for gastric lavage. ... Activated Charcoal. Adults, 50-100 g; children, 15-30 g in aqueous or sorbital slurry, after emesis is induced or into the gastric tube after lavage. Cathartic. Magnesium sulfate or sodium sulfate; adult, 30 g children, 250 mg/kg. No studies on efficacy are available with this group of drugs. Elimination enhancement. In view of the extensive protein binding and extensive volume of distribution of some drugs of this group, it is unlikely that hemodialysis or peritoneal dialysis would be effective. In any case, no studies exist to demonstrate such efficacy. Most cases are amenable to good supportive therapy. Antidotes. There are no antidotes. /alpha-Adrenergic blockers/|Recommended treatment for phenoxybenzamine overdose includes: treatment of circulatory failure, either by placing the patient in the recumbent position with legs elevated or additional measures if shock is present. The usual pressor agents are not effective; epinephrine should not be used because of the risk of further hypotension. Intravenous administration of levarterenol bitartrate may be useful.

... RESULTS OF ALPHA-RECEPTOR BLOCKADE INCL MIOSIS, NASAL STUFFINESS, & INHIBITION OF EJACULATION. EFFECTS NOT CLEARLY RELATED TO BLOCKADE ARE LOCAL TISSUE IRRITATION, SEDATION, & GENERALIZED FEELING OF WEAKNESS & TIREDNESS. LOCAL IRRITATION IS ... INVOLVED IN NAUSEA & OCCASIONAL VOMITING THAT MAY FOLLOW LARGE ORAL DOSES, PARTICULARLY IF ADMIN ON AN EMPTY STOMACH.|PHENOXYBENZAMINE ... MAY PRODUCE SLIGHT CONJUNCTIVAL HYPEREMIA ASSOC WITH NASAL STUFFINESS & SLIGHT PTOSIS. IT HAS HAD NO ADVERSE EFFECT IN GLAUCOMA, BUT RATHER HAS OCCASIONALLY BEEN SUSPECTED TO REDUCE INTRAOCULAR PRESSURE SLIGHTLY.|CONTACT DERMATITIS FROM PHENOXYBENZAMINE HYDROCHLORIDE OCCURRED IN A WOMAN LAB TECHNICIAN. CROSS-SENSITIVITY TO RELATED CMPD MAY BE DUE TO THE CHLOROETHYLAMINE MOIETY OF THE MOLECULE. /PHENOXYBENZAMINE HYDROCHLORIDE/|... PHENOXYBENZAMINE ... CAN STIMULATE THE CNS TO CAUSE NAUSEA, VOMITING, HYPERVENTILATION, MOTOR EXCITABILITY, & EVEN CONVULSIONS, PARTICULARLY WHEN A RELATIVELY LARGE DOSE IS RAPIDLY INJECTED IV. IN MAN, A CHARACTERISTIC LOSS OF TIME PERCEPTION MAY OCCUR.

Dibenylene

PHENOXYBENZAMINE HYDROCHLORIDE, USP (DIBENZYLINE), IS AVAILABLE FOR ORAL USE IN 10-MG CAPSULES; AMPULS FOR IV USE (100 MG OF DRUG IN 2 ML) ARE AVAILABLE FOR INVESTIGATIONAL PURPOSES. /PHENOXYBENZAMINE HYDROCHLORIDE/|Phenoxybenzamine hydrochloride is available in the US as a NF grade containing 98.0-101.0% active ingredient calculated on the dried basis. It is also available in 10 mg capsules containing 90.0-110.0% of the labelled amount of phenoxybenzamine hydrochloride. /Phenoxybenzamine hydrochloride/

Phenoxybenzamine is available only as the hydrochloride.|Phenoxybenzamine hydrochloride has been produced by a single company in the USA since 1953, in an undisclosed amount. /Phenoxybenzamine hydrochloride/

PHENOXYBENZAMINE CAN BE DETERMINED BY THIN-LAYER CHROMATOGRAPHY USING A SOLVENT SYSTEM OF HEPTANE, CHLOROFORM & METHANOL. THE PHENOXYBENZAMINE HYDROCHLORIDE CONTENT OF A CHLOROFORM SOLN CAN BE DETERMINED BY ULTRAVIOLET SPECTROMETRY.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals