PhenoxybenzamineHCl (0-100 μM; 96 h) strongly suppresses the growth of U251 and U87MG cells [2]. PhenoxybenzamineHCl (10μM; 24 hours or 72 hours) inhibits the migration and invasion of U251 and U87MG cells [2]. Phenoxybenzamine Hydrochloride (10 μM; 12 h) stimulates LINGO-1 and inhibits the TrkB-Akt pathway [2]. Phenoxybenzamine (0.1 μM-1 mM; 0-16 hours) inhibits hippocampus cell death during oxygen and glucose deprivation [3]. Cell proliferation experiment [2]

Mice administered subcutaneously with phenoxybenzamine hydrochloride (20 nM) twice a day for 26 days demonstrate anticancer effects [2]. In a rat model of severe traumatic brain injury, phenoxybenzamine (1.0 mg/kg; intravenously; once daily for 30 days) shows neuroprotective benefits [3].

Cell proliferation experiment [2]
Cell Types: U251 and U87MG cell
Tested Concentrations: 0.1, 1, 10, 50 and 100 μM
Incubation Duration: 96 h
Experimental Results: Cell proliferation was Dramatically inhibited, the inhibition rate of U251 cells was 26.5%, and the inhibition rate of U251 cells was 26.5%. is 27.3% for U87MG cells at a concentration of 10 μM.

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Cell migration experiment [2]
Cell Types: U251 and U87MG Cell
Tested Concentrations: 10 μM
Incubation Duration: 24 h
Experimental Results: Obvious migration inhibition was observed, and the inhibition rates of U251 and U87MG were 28.6% and 39.8% respectively. Cell invasion analysis [2]
Cell Types: U251 and U87MG Cell
Tested Concentrations: 10 μM
Incubation Duration: 72 h
Experimental Results: The invasion ability of U251 and U87MG was Dramatically weakened, and the number of invasive cells per field of view dropped from 365/field to 132/field for U251. field (36.2%), U87MG is 444/field to 298/field (67.1%).

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Western Blot Analysis [2]
Cell Types: U251
Tested Concentrations: 10 μM
Incubation Duration: 12 h
Experimental Results: TrkB,

Animal/Disease Models: nude mice, U87MG tumor model [2]
Doses: 20 nM
Route of Administration: subcutaneous injection, 2 days apart, for 26 days.
Experimental Results: tumor cell reduction.

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Animal/Disease Models: Male Wistar rat (350–500 g), traumatic brain injury (TBI) model [3]
Doses: 1.0 mg/kg
Route of Administration: intravenously (iv) (iv)(iv), one time/day for 30 days
Experimental Results: Neurological severity score (NSS) and foot error scores on days 14, 21, and 30. Reduce cognitive impairment associated with severe TBI and reduce expression of pro-inflammatory genes.

Absorption, Distribution and Excretion
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/

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Metabolism / Metabolites
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/

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Biological Half-Life
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.

Interactions
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.

[1]. Urapidil in the preoperative treatment of pheochromocytomas: a safe and cost-effective method. World J Surg. 2013 May;37(5):1141-6.

[2]. Anti-tumor activity of phenoxybenzamine hydrochloride on malignant glioma cells. Tumour Biol. 2016 Mar;37(3):2901-8.

[3]. Phenoxybenzamine is neuroprotective in a rat model of severe traumatic brain injury. Int J Mol Sci. 2014 Jan 20;15(1):1402-17.

Phenoxybenzamine can cause cancer according to an independent committee of scientific and health experts.
Phenoxybenzamine is an aromatic amine.
An alpha-adrenergic antagonist with long duration of action. It has been used to treat hypertension and as a peripheral vasodilator.
Phenoxybenzamine is an alpha-Adrenergic Blocker. The mechanism of action of phenoxybenzamine is as an Adrenergic alpha-Antagonist.
Phenoxybenzamine is a synthetic, dibenzamine alpha adrenergic antagonist with antihypertensive and vasodilatory properties. Phenoxybenzamine non-selectively and irreversibly blocks the postsynaptic alpha-adrenergic receptor in smooth muscle, thereby preventing vasoconstriction, relieving vasospasms, and decreasing peripheral resistance. Reflex tachycardia may occur and may be enhanced by blockade of alpha-2 receptors which enhances norepinephrine release. Phenoxybenzamine is reasonably anticipated to be a human carcinogen.
An alpha-adrenergic antagonist with long duration of action. It has been used to treat hypertension and as a peripheral vasodilator.
See also: Phenoxybenzamine Hydrochloride (has salt form).

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

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Mechanism of Action
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.

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Therapeutic Uses
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.

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Drug Warnings
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/

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Pharmacodynamics
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.

C18H22CLNO

303.83

303.139

59-96-1

Phenoxybenzamine hydrochloride;63-92-3;Phenoxybenzamine-d5 hydrochloride;1329838-45-0;Phenoxybenzamine (benzyl-2,3,4,5,6-d5) (hydrochloride);1398065-71-8;Phenoxybenzamine-d5;1309283-11-1

4768

CRYSTALS FROM PETROLEUM ETHER

1.102g/cm3

381.5ºC at 760mmHg

38-40ºC

184.5ºC

1.559

4.194

0

2

8

21

262

0

C(N(CCCl)C(C)COC1C=CC=CC=1)C1C=CC=CC=1

QZVCTJOXCFMACW-UHFFFAOYSA-N

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

N-benzyl-N-(2-chloroethyl)-1-phenoxypropan-2-amine

Phenoxybenzamine NSC 37448 NSC37448 NSC-37448A688 A 688A-688

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)