β adrenergic receptor ( IC50 = 12 nM )

Propranolol hydrochloride (orally administration; 40 mg/kg; daily) dramatically decreases the vessel diameter in comparison to the vehicle-treated implants and increases the proportion of cells expressing phosphorylated ERK1/2 in the IH Matrigel implant[4].

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Propranolol Affects Vascular Development in a Xenograft Mouse Model of IH [4]
To assess how propranolol affects HemSCs and IH development in vivo, we adapted a previously described mouse model [20]. In the IH mouse model, HemSCs resuspended in Matrigel are implanted subcutaneously in immunocompromised mice, and IH vessel development progresses over 3 weeks. The mice were treated with propranolol or vehicle 40 mg/kg daily. Using the surface area conversion factor of 1/12 [37–39], the mice received a human equivalent dose of 3.3–4.8 mg/kg daily. IH Matrigel implants from propranolol-treated mice had reduced blood flow at 14 and 21 days after implantation, measured by Doppler ultrasound, compared with vehicle (data not shown; Fig. 7A). Histological analysis of the 21-day IH Matrigel implants (Fig. 7B) demonstrated that propranolol did not affect blood vessel density (Fig. 7C) but did significantly reduce the vessel diameter relative to the vehicle-treated implants (Fig. 7D). The reduced vessel caliber correlated with a loss of Doppler-detectable flow in the propranolol treatment group. Propranolol also significantly increased the number of cells that expressed phosphorylated ERK1/2 within the IH Matrigel implant (Fig. 7E), consistent with the results from our in vitro studies. Thus, propranolol improved vessel development in the IH mouse model that correlated with MAPK pathway activation. [4]

Caspase-3 Assay [4]
HemSCs were seeded in EGM-2 with 20% FBS media and allowed to settle for 4 hours. HemSCs were treated at increasing concentrations of propranolol in SFM with 0.1% FBS for 24 hours. The protein lysates were collected, and caspase-3 activation was quantified using the Caspase-3 Human ELISA Kit.

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cAMP Assay [4]
The cAMP levels in HemSCs were determined using the LANCE Ultra cAMP kit. The HemSCs were washed and resuspended in the provided stimulation buffer (Hanks’ balanced saline solution, bovine serum albumin, isobutylmethylxanthine, HEPES buffered saline solution) and seeded (1,000 per well) on a 96-well plate. The cells were then treated with drugs for 30 minutes. Tracer and ULight-anti-cAMP working solutions were added and incubated at room temperature for 1 hour. The time-resolved fluorescence resonance energy transfer signal was determined using the EnVision Multilabel Plate Reader. cAMP levels were determined using a standard curve, and data were interpolated using a comprehensive curve fitting (nonlinear regression) and Prism. Each condition was used in triplicate, and the experiments were performed at least two times. A representative experiment is presented in the figures. To determine whether βARs are coupled to Gαs or Gαi in HemSCs, the cells were treated with isoprenaline, with or without 10 μM forskolin, over a 6-log dose range by serial dilutions with water for 30 minutes. Next, the cAMP levels were measured as described to determine whether βARs were coupled to Gαs or Gαi in HemSCs.

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ERK1/2 Western Blotting [4]
Cells were cultured on fibronectin-coated plates and treated with various concentrations of βAR antagonists and incubated for 30 minutes. The cells were lysed in TENT buffer (50 mM Tris [pH 8.0], 2 mM EDTA, 150 mM NaCl, 1% Triton-X-100) with 1% Halt Protease Inhibitor, 1% phosphatase inhibitor, and 0.5% sodium orthovanadate. Western blotting was performed for ERK1/2 (p44/42, 1:1,000) and pERK1/2 (P-p44/42, 1:500). The blots were stripped and then probed for α-tubulin (1:10,000) to normalize protein loading. Experiments were performed at least three times, and a representative experiment is presented in the figures.

In vitro, the neonatal mice cardiomyocytes (NMCMs) are treated with different drugs of different concentration, including isoproterenol (0, 1, 2.5, 5, 10, 20, and 50 μM); amiodarone (0, 1, 2.5, 5, 10, 20, and 50 μM); metoprolol (0, 10, 20, 30, 50, 100, 150, and 200 μM); propranolol (0, 10, 20, 40, 50, and 100 μM); lidocaine (0, 1, 2.5, 5, 10, 20, and 50 μM); verapamil(0, 1, 2.5, 5, 10, 20, and 50 μM);ivabradine (0, 1, 2, 3, 5, 10, and 20 μM). And the concentrations of drugs that promote CMs proliferation most significantly are chosen for subsequent experiments, including isoproterenol (10 μM), amiodarone (5 μM), metoprolol (20 μM), propranolol (20 μM), lidocaine (5 μM), verapamil (2.5 μM), ivabradine (3 μM) for NMCMs, NMCFs, and hPSC-CM.

A xenograft mouse model of IH (infantile hemangiomas) with HemSC cells
40 mg/kg
Orally administration; 40 mg/kg; daily

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IH Mouse Model [4]
To study the effects of propranolol on HemSCs in vivo, a xenograft mouse model of IH was used as previously described. In brief, 1.5 × 106 HemSCs (n = 2) suspended in 200 µL of Corning Matrigel Matrix was implanted subcutaneously into the flanks of female 6–8-week-old NCrNude immunodeficient mice. Propranolol, which was provided in drinking solution, was initiated the day of IH xenografting. Propranolol was diluted to 270 µM in 5% dextrose water (vehicle), and daily consumption was measured to calculate the treatment dosage, which averaged 40 mg/kg daily. Blood flow within the IH Matrigel implant was analyzed using a VEVO 2100 Ultrasound Imaging System on a Doppler setting on days 14 and 21 of IH development. The mice were anesthetized with isoflurane and restrained in a supine position. The region of interest was fully scanned, with the transducer positioned at its largest longitudinal section over the implant to optimize the spatial resolution of the image, maximizing the detail. Next, two-dimensional images were captured in uniform steps of 0.05 mm. The images of blood flow were analyzed using software provided by VisualSonics. The mice were sacrificed after 21 days. The Matrigel implants were collected and fixed overnight at 4°C in 10% formalin. The implants were dehydrated and embedded in paraffin for histological analysis. Vessel density and caliber were counted in 3–4 HPFs per implant (n = 4 for each group). Vessel density was determined as the number of vessels (whether longitudinally or axially oriented) per HPF. The vessel diameter was measured according to the orientation. For longitudinally oriented vessels, the width was measured at three points and averaged, and the cross-section (axial) vessels were measured once. Vessels were identified as tubular structures with erythrocytes within.

Absorption, Distribution and Excretion
Studies in man and experimental animals indicate that rapid hepatic clearance is responsible for appearance of only trace amount of unmetabolized propranolol in blood after small oral doses. With larger doses, blood levels are linearly related to dose, suggesting saturation of hepatic metabolic system.
Propranolol is almost completely absorbed from the GI tract; however, plasma concentrations attained are quite variable among individuals. There is no difference in the rate of absorption of the 2 isomers of propranolol. Propranolol appears in the plasma within 30 min, and peak plasma concentrations are reached about 60-90 min after oral administration of the conventional tablets. The time when peak plasma concentrations are reached may be delayed, but concentrations are not necessarily lowered, when the drug is administered with food. Oral bioavailability of the drug may be increased in children with Down's syndrome; higher than expected plasma propranolol concentrations have been observed in such children. Bioavailability of a single 40-mg oral dose of propranolol hydrochloride as a conventional tablet or oral solution reportedly is equivalent in adults.
Propranolol hydrochloride is slowly absorbed following administration of the drug as extended release capsules, and peak blood concentrations are reached about 6 hr after administration. When measured at steady state over a 24 hr period, the area under the plasma concentration time curve for the extended release capsules is about 60-65% of the plasma concentration time curve for a comparable divided daily dose of the conventional tablets. The lower plasma concentration time curve is probably caused by the slower rate of absorption of the drug from the extended release capsules with resultant greater hepatic metabolism. After administration of a single dose of propranolol as the extended release capsules, blood concentrations are fairly constant for about 12 hr and then decline exponentially during the following 12 hr.
Following iv administration of propranolol, the onset of action is almost immediate. Animal studies indicate that propranolol is rapidly absorbed after im administration.
For more Absorption, Distribution and Excretion (Complete) data for PROPRANOLOL HYDROCHLORIDE (12 total), please visit the HSDB record page.

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Metabolism / Metabolites
Besides ... 4-hydroxypropranolol and naphthoxylacetic acid, 6 new urinary metabolites have... been identified... /which are/ n-deisopropylpropranolol; 1-(alpha-naphthoxy)-2,3-propyleneglycol; ring hydroxylated 1-(alpha-naphthoxy)-2,3-propyleneglycol; alpha-naphthoxyacetic acid; alpha-naphthol and 1,4-dihydroxynaphthalene.
Isopropylamine and hexadeuteriated isopropylamine have been identified as urinary metabolites of propranolol and hexadeuteriated propranolol, respectively; this is believed to be 1st recorded example of single-step oxidative deamination of n-isopropylamine compound.
During initial oral therapy (but not during iv or chronic oral therapy), an active metabolite, 4-hydroxypropranolol, is formed. 4-Hydroxypropranolol has about the same beta-adrenergic blocking potency as does propranolol and may be present in plasma in amounts about equal to propranolol. This metabolite is eliminated more rapidly than propranolol and is virtually absent from the plasma 6 hr after oral administration of the drug. Results of one study indicate that after iv administration or chronic oral administration of propranolol, 4-hydroxypropranolol is not formed to a substantial extent, and beta-adrenergic blocking activity is more closely reflected by propranolol concentrations. Individual variations in ability to hydroxylate propranolol to the active metabolite may also exist. In addition, some other metabolites of propranolol may possess antiarrhythmic activity without beta-adrenergic blocking activity.
Propranolol is almost completely metabolized in the liver and at least 8 metabolites have been identified in urine. Only 1-4% of an oral or iv dose of the drug appears in feces as unchanged drug and metabolites.

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Biological Half-Life
When usual therapeutic doses of propranolol are administered chronically, the half-life ranges from 3.4-6 hr. Single dose studies generally have shown a shorter half-life of 2-3 hr.

Toxicity Summary
IDENTIFICATION: Propranolol is a class II antiarrhthmic drug which be longs to the beta-andrenergic blocking agents. Propranol hydrochloride is a white, odorless white crystalline powder. It is soluble in alcohol; slightly soluble in chloroform; practically insoluble in ether. Cardiovascular diseases: Propranolol, a non cardioselective beta-blocker, is mostly used in the treatment of hypertension, angina, for the prevention of re-infarction in patients who have suffered from myocardial infarction. It is also used to control symptoms of anxiety and in the treatment of supraventricular tachycardia, hypertrophic obstructive and cardiomyopathy. Endocrine disorders: In hyperthyroidism and thyrotoxic crisis; together with alpha-blocking agents in the preoperative treatment of pheochromocytoma. Hepatic diseases: Prevention of hemorrhage in portal hypertension Neurological disorders: Propranolol has also been used in the treatment of extrapyramidal disorders and in the prophylaxis of migraine headache. Anxiety disorders: Propranolol may be used in acute stress reactions, somatic anxiety and panic reactions, but its value is questioned. HUMAN EXPOSURE: Main risks and target organs: Beta-blockers compete with endogenous and/or exogenous beta-adrenergic agonists. Propranolol is not cardioselective and it has no intrinsic sympathomimetic activity. It has membrane stabilizing properties and is highly lipid soluble. At toxic doses, propranolol has a pronounced negative chronotropic and inotropic effect and also a quinidine like effect on the heart. The cardiovascular system is the main target organ. Propranolol decreases sinus rate, atrio-ventricular conduction, intraventricular conduction and cardiac contractility. Central nervous system toxicity (coma and convulsions) may also occur because of its high liposolubility.Summary of clinical effects: Toxicity occurs within 1 to 2 hours following ingestion but the delay in onset may vary according to the formulation. Symptoms may include: Cardiovascular disturbances: bradycardia, atrioventricular block of varying degrees, intraventricular block, hypotension, cardiogenic shock and pulmonary edema. Neurological symptoms: coma and convulsions. Respiratory depression and apnea. Cardiovascular collapse and apnea may occur suddenly. Patients with underlying cardiovascular disease are predisposed to the adverse cardiac effects of propranolol. Propranolol may induce bronchospasm in asthmatic patients. Contraindications: Absolute: asthma, congestive cardiac failure, atrio-ventricular block, bradycardia and treatment with amiodarone. Relative: Raynaud's disease, diabetes mellitus. Routes of entry: Oral: Ingestion is the most frequent cause of poisoning Inhalation: no case has been reported. The effect of 10 mg propranolol given by nasal route is rapid and equivalent to the intravenous route. Parenteral: No case of overdoses has been reported. Cardiovascular symptoms have been reported after therapeutic administration. Absorption by route of exposure: After oral administration, propranolol is almost completely and rapidly absorbed from the gastrointestinal tract. However, because of the high first-pass metabolism and hepatic tissue binding, the absolute bioavailability is only about 30% and varies greatly between individuals. Peak plasma concentration occurs one to two hours after administration. After administration of the sustained release formulation, the peak plasma concentration occurs 7 hours after absorption. Distribution by route of exposure: About 90 to 95 % of the drug is bound to plasma proteins. Propranolol is highly lipophilic: it crosses the blood-brain barrier and the placenta. Biological half-life by route of exposure: After oral administration, propranolol undergoes saturable kinetics. The plasma half-life is 3 to 6 hours and is about 12 hours with the sustained release forms. The total body clearance is 800 mL/minute/1.73 m2. After overdose, the plasma half-life is prolonged. One study reported a half-life of 16 hours. In two cases reported, the half-life was 13.8 and 8.3 hours. In five cases, the mean plasma half-life was 10.5 hours (range: 5.1 to 17). Metabolism: Propranolol is extensively metabolized by the liver. At least one of the metabolites, the 4-hydroxypropranolol, is biologically active. The hepatic metabolism is saturable and bioavailability may be increased in overdoses. Elimination by route of exposure: After a single oral dose, propranolol is completely eliminated in 48 hours, mainly by hepatic metabolism. Less than 0.5 % is excreted unchanged in urine. The renal clearance is 12 mL/kg/minute. About 20% of the dose is eliminated in urine mainly as glucuronide conjugates. Propranolol is excreted in breast milk at a concentration of 50% that of blood. Mode of action Toxicodynamics: Propranolol is a non cardioselective beta-blocker with no intrinsic sympathomimetic action. It has membrane stabilizing activity and is highly lipid soluble. At toxic doses, propranolol has a pronounced negative chronotropic and inotropic effect and a quinidine-like effect on the heart: the result is a reduction of the heart rate, a decrease of the sino-atrial and atrioventricular conduction, a prolongation of the intraventricular conduction and a decrease of cardiac output. Blockade of beta-2 receptors may cause bronchospasm and hypoglycemia. Given its high lipid solubility, propranolol crosses the blood-brain barrier and may cause coma and convulsions. Pharmacodynamics: Beta-blocking agents compete with endogenous and/or exogenous beta-adrenergic agonists. Their specific effects depend on their selectivity for beta-1 receptors (located in the heart) or beta-2 receptors (located in bronchi, blood vessels, stomach, gut, uterus). Beta-blockers are classified according to their cardioselectivity, membrane stabilizing effect, intrinsic sympathomimetic effect and lipid solubility. At therapeutic doses, propranolol slightly decreases heart rate (15%), supraventricular conduction and cardiac output (15 to 20%). Cardiac work and oxygen consumption are also decreased. Propranolol decreases the secretion of renin. The pharmaceutical form of propranolol is a racemate: the dextrorotary isomer accounts for most of the beta-blocking effect, whereas the levorotary isomer has a predominantly membrane stabilizing effect. Toxicity: Human data: Adults: Propranolol toxicity shows individual variations which may be due to an underlying cardiac disease, to the ingestion of other cardiotoxic drugs and to variations in first-pass metabolism. Children: Ingestion of 70 mg by a 2 year old child produced drowsiness, second degree atrioventricular block and hypoglycemia. Ingestion of 100 mg by a 5-year-old child produced drowsiness, delirium and hallucinations. Interactions: Decreased bioavailability: Antacids decrease the gastric absorption of propranolol. Barbiturates, phenytoïn and rifampicin increase the first-pass clearance of propranolol by hepatic enzyme induction. Increased bioavailability: Plasma propranolol concentrations may be increased up to 50% by histamine H2 antagonists and oral contraceptives, which decrease hepatic metabolism by enzyme inhibition. Diminished pharmacodynamic effects: Non-steroidal anti-inflammatory drugs decrease the antihypertensive effect of propranolol. Nifedipine might exacerbate the symptoms of beta-blocker withdrawal. Enhanced pharmacodynamic effects: Digitalis, amiodarone, verapamil and diltiazem may increase bradycardia due to propranolol. Verapamil, prenylamine, flecainide and disopyramide enhance the negative inotropic effect of propranolol. Main adverse effects: Numerous adverse effects during propranolol treatment have been reported. Cardiovascular: sinus bradycardia, atrioventricular block, hypotension, increase of left ventricular failure, cardiogenic shock, intermittent claudication. Respiratory: bronchospasm, exacerbation of asthmatic symptoms in known asthmatics, pulmonary edema. Central nervous system: depression, psychosis, convulsions, hallucinations. Musculoskeletal: muscle weakness, aggravation of myasthenia gravis, peripheral neuropathy. Gastrointestinal: vomiting, diarrhea, dry mouth. Endocrine and metabolic: hypoglycemia, hyperkalemia, hypothyroidism, sexual dysfunction (impotence). Dermatological: urticaria, exfoliative dermatitis. Hematological: agranulocytosis (immunologic reaction), thrombocytopenia. Teratogenicity: a case of tracheoesophageal fistula in a newborn of a mother treated with propranolol during the pregnancy has been reported. However, a teratogenic effect of propranolol has not been confirmed. Pregnancy: hypoglycemia and lethargy have been reported in newborn from mothers treated with propranolol before delivery. Others: propranolol treatment may potentiate anaphylactic shock. Clinical effects: Acute poisoning: Ingestion: The severity of propranolol poisoning is due to its cardiotoxicity and depends on the dose ingested, the presence of underlying cardiac disease and concomitant ingestion of other cardiotoxic drugs. Symptoms and signs appear within one to two hours and may include the following: Cardiovascular effects: bradycardia, hypotension, cardiogenic shock. The ECG may show nodal rhythm, atrioventricular block and QRS widening. CNS effects: lethargy, coma and convulsions and mydriasis. Hypoventilation resulting from severe shock. Parenteral exposure: Cardiovascular effects: bradycardia, hypotension, cardiogenic shock. The ECG may show nodal rhythm, atrioventricular block and QRS widening CNS effects: lethargy, coma and convulsions, mydriasis Hypoventilation resulting from severe shock. Course, prognosis, cause of death: Patients who survive 48 hours after acute poisoning or who have not developed cardiac arrest before admission are likely to recover. Death may occur from cardiac asystole which is noted by hypoxemia. The prognosis depends on the dose ingested and is worse in patients with an underlying cardiac disease and in those who have ingested other cardiotoxic drugs. Systematic description of clinical effects: Cardiovascular: Acute: Cardiovascular symptoms are the major features of propranolol poisoning. Bradycardia is the commonest symptom (present in 60 to 90% of cases) and occurs soon after ingestion. Hypotension is observed in about 50 to 70% of the cases. Hypotension and shock are due to decreased cardiac output and vasodilatation. Cardiac arrest may occur within 1 to 2 hours of ingestion. Cardiac arrest has been reported to occur in 45 minutes following an over dose propranolol by a 60 year old man. ECG changes are always present in symptomatic poisoning: sinus or nodal bradycardia, atrioventricular block (1st to 3rd degree) are the most common. Widening of the QRS interval, bundle branch block or increased QT interval are less frequently observed. Respiratory: Acute: Respiratory depression and apnea is mostly associated with severe shock and is due to cerebral hypoxia. Pulmonary edema may occur, especially in patients with a previous compromised cardiac function. Bronchospasm may occur in susceptible patients. Neurological: CNS: Acute: Lethargy, drowsiness, agitation, delirium, hallucinations and mydriasis may be observed. Coma is usually only seen in patients with cardiovascular collapse. Convulsions have been reported after ingestion of large doses. Convulsions may be due to hypotension or to a direct effect of propranolol (membrane stabilizing effect). Chronic: Fatigue, CNS depression, hallucinations and psychosis have been reported. Autonomic nervous system: Acute: Effects of beta-receptor blockade. Chronic: Effects of beta-receptor blockade. Skeletal and smooth muscle: Chronic: Muscular fatigue may be observed. Gastrointestinal: Acute: vomiting, nausea may be seen; spasm of the lower oesophageal sphincter has been reported in two cases. A case of mesenteric ischemia following propranolol overdose has been reported. Eye, ear, nose, throat: local effects: Acute: Mydriasis and diplopia may be noted. Metabolic: Acid-base disturbances: Metabolic acidosis may occur in severe poisoning with shock. Fluid and electrolyte disturbances: Hypokalemia or a hyperkalaemia have been reported rarely. Others: Hypoglycemia was reported in two cases of poisoning in children.

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because of the low levels of propranolol in breastmilk, amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants. Studies during breastfeeding have found no adverse reactions in breastfed infants clearly attributable to propranolol. No special precautions are required. Propranolol has been used successfully in cases of persistent pain of the breast during breastfeeding.
◉ Effects in Breastfed Infants
A study of mothers taking beta-blockers during nursing found a numerically, but not statistically significant increased number of adverse reactions in those taking any beta-blocker. Although the ages of infants were matched to control infants, the ages of the affected infants were not stated. Of 8 mothers taking propranolol, one reported sleepiness in her breastfed infant, but she was also taking other unspecified drugs for hypertension.
A case of bradycardia in a 2-day-old breastfed infant was reported to the French pharmacovigilance system. However it is not clear from the report whether the mother had been taking propranolol near term and might have transmitted the drug to the infant transplacentally.
◉ Effects on Lactation and Breastmilk
Relevant published information on the effects of beta-blockade or propranolol during normal lactation was not found as of the revision date. A study in 6 patients with hyperprolactinemia and galactorrhea found no changes in serum prolactin levels following beta-adrenergic blockade with propranolol.

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Interactions
Propranolol antagonizes cardiac stimulation that may limit effectiveness of hydralazine, and combination has been shown to be more effective than either drug alone.
Neuromuscular blockade produced by tubocurarine was prolonged in 2 thyrotoxic patients receiving high doses (120 mg/day for 14 days) of propranolol. ...Decamethonium and succinylcholine have been shown to interact with propranolol in similar manner... in animals.
Propranolol increased acute CNS toxicity of ether, hexobarbital, morphine and urethane in mice.
Stimulatory effect of epinephrine on heart is blocked by propranolol. If epinephrine is administered to patient receiving propranolol, reflex tachycardia may result, /SRP: due to fall in blood pressure because of beta blockade on blood vessels/.
For more Interactions (Complete) data for PROPRANOLOL HYDROCHLORIDE (16 total), please visit the HSDB record page.

[1]. Distinct signaling profiles of beta1 and beta2 adrenergic receptor ligands toward adenylyl cyclase and mitogen-activated protein kinase reveals the pluridimensionality of efficacy. Mol Pharmacol . 2006 Nov;70(5):1575-84.

[2]. Evidence against beta-adrenoceptor blocking activity of diltiazem, a drug with calcium antagonist properties. Br J Pharmacol. 1980 Aug;69(4):669-73.

[3]. Propranolol. Profiles Drug Subst Excip Relat Methodol. 2017;42:287-338.

[4]. Propranolol Targets Hemangioma Stem Cells via cAMP and Mitogen-Activated Protein Kinase Regulation. Stem Cells Transl Med. 2016 Jan;5(1):45-55.

Therapeutic Uses
Adrenergic beta-Antagonists; Anti-Anxiety Agents; Anti-Arrhythmia Agents; Antihypertensive Agents; Sympatholytics; Vasodilator Agents
/SRP: Former use/: Propranolol has proven to be effective in numerous cases in which digitalis, with or without quinidine and/or procainamide, failed to reduce ventricular rate, and in cases of paroxysmal atrial tachycardia attributed to digitalis toxicity.
Propranolol is also used in hypertrophic obstructive cardiomyopathies. In these conditions forceful contraction of myocardium along a ventricular outflow tract can greatly increase outflow resistance, particularly during exercise. .../It/ is sometimes useful in management of tachycardia and arrhythmias in patient with pheochromocytoma.
Medication (Vet): ...Atropine in conjunction with propranolol /was found/ to be useful in treatment of oleander poisoning.
For more Therapeutic Uses (Complete) data for PROPRANOLOL HYDROCHLORIDE (25 total), please visit the HSDB record page.

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Drug Warnings
.../Propranolol/ is relatively contraindicated in ...hay fever, cardiogenic shock, congestive heart failure, right ventricular failure secondary to pulmonary hypertension, and when myocardial depressant anesthetics, tricyclic antidepressants, or oral hypoglycemics are used.
Propranolol (1% solution) used as eye-drops .../per 1 report/, caused intense pain lasting as long as 15 min and induced hyperemia and slight miosis, but according to others these eye-drops have been well tolerated by most patients in use up to 4 times/day for 3-4 months, causing burning sensations and conjunctival hyperemia in only 8/47 eyes.
Contraindicated in patients with cardiogenic shock, sinus bradycardia and greater than first degree block, bronchial asthma, and congestive heart failure. Adverse reactions include weakness, light headedness, depression, bradycardia, paresthesia of hands, arterial insufficiency (e.g., Raynaud type), nausea, and diarrhea. Use is best avoided in patients with bronchospastic diseases and therapy in diabetic patients must be closely monitored.
After sudden cessation of propranolol therapy in some patients treated for angina, increased frequency, duration, and severity of angina episodes have occurred, often within 24 hr. These episodes are unstable and are not relieved by nitroglycerin. Acute and sometimes fatal myocardial infarction and sudden death have also occurred after abrupt withdrawal of propranolol therapy in some patients treated for angina. In hypertensive patients, sudden cessation of propranolol has produced a syndrome similar to florid thyrotoxicosis, characterized by tenseness, anxiety, tachycardia, and excessive perspiration; these symptoms occurred within one week of cessation of the drug and were relieved by reinstituting propranolol therapy.
For more Drug Warnings (Complete) data for PROPRANOLOL HYDROCHLORIDE (31 total), please visit the HSDB record page.

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1 The isolated spontaneously beating atria of the rat, diltiazem (0.01 to 0.1 microM) shifted the atrial rate concentration-response curves to isoprenaline to the right in a non-parallel manner and depressed their maxima. Under the same experimental conditions, (+/-)-propranolol (0.03 to 0.1 microM) behaved as a competitive beta-adrenoceptor antagonist. 2 Whereas (+/-)-propranolol (IC50 = 12 nM) and isoprenaline (IC50 = 0.9 microM) inhibited (-)-[3H]-dihydroalprenolol binding to rat brain membrane preparations, diltiazem failed to do so in concentrations up to 10 microM. 3 Diltiazem but not (+/-)-propranolol, antagonized the positive chronotropic responses to calcium in spontaneously beating rat atria. 4 It is proposed that diltiazem inhibited the tachycardia induced by isoprenaline through an effect on calcium which may be an essential modulator of the sequence of events linking the beta-adrenoceptor activation and heart rate response.[2]

C16H22CLNO2

295.8

331.11

C, 64.97; H, 7.50; Cl, 11.98; N, 4.74; O, 10.82

318-98-9

(S)-(-)-Propranolol hydrochloride; 4199-10-4; Propranolol; 525-66-6; Propranolol-d7 hydrochloride; 1613439-56-7; Propranolol-d7 (ring-d7); 344298-99-3

62882

White to off-white solid powder

434.9ºC at 760mmHg

163-165 °C(lit.)

216.8ºC

3.77

3

3

6

20

257

0

OC(CNC(C)C)COC1=CC=CC2=CC=CC=C12.Cl

ZMRUPTIKESYGQW-UHFFFAOYSA-N

InChI=1S/C16H21NO2.ClH/c1-12(2)17-10-14(18)11-19-16-9-5-7-13-6-3-4-8-15(13)16;/h3-9,12,14,17-18H,10-11H2,1-2H3;1H

1-naphthalen-1-yloxy-3-(propan-2-ylamino)propan-2-ol;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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

Solubility in Formulation 1: 25 mg/mL (84.52 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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Solubility in Formulation 2: 5%DMSO + Corn oil: 3.0mg/ml (10.14mM)

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