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
Human and animal studies have shown that after small oral doses, only trace amounts of unmetabolized propranolol appear in the blood, primarily due to rapid hepatic clearance. Higher doses result in a linear relationship between blood concentration and dosage, indicating that the hepatic metabolic system has reached saturation. Propranolol is almost completely absorbed from the gastrointestinal tract; however, there is significant inter-individual variation in plasma concentration. The absorption rates of the two isomers of propranolol are not different. After oral administration of a standard tablet, propranolol enters the plasma within 30 minutes, reaching peak plasma concentration in approximately 60-90 minutes. When taken with food, the time to peak plasma concentration may be delayed, but the drug concentration does not necessarily decrease. Oral bioavailability may be increased in children with Down syndrome; higher-than-expected plasma propranolol concentrations have been observed in these children. The bioavailability of a single oral dose of 40 mg propranolol hydrochloride tablets or oral solution in adults has been reported to be comparable. Propranolol hydrochloride extended-release capsules are absorbed slowly after administration, reaching peak plasma concentration approximately 6 hours later. Measured at a steady-state level over 24 hours, the area under the plasma concentration-time curve (AUC) of the extended-release capsules was approximately 60-65% of that of conventional tablets administered in divided doses at the same dosage. The lower AUC is likely due to the slower absorption rate of the extended-release capsules, leading to increased hepatic metabolism. Following a single dose of the extended-release capsule, plasma concentrations remained relatively stable for approximately 12 hours, followed by an exponential decline over the next 12 hours.
Intravenous administration of propranolol has an almost immediate onset of action. Animal studies have shown rapid absorption following intramuscular administration of propranolol.
For more complete data on the absorption, distribution, and excretion of propranolol hydrochloride (12 metabolites), please visit the HSDB records page.
Metabolisms/Metabolites
In addition to 4-hydroxypropranolol and naphthoxyacetic acid, six new urinary metabolites were identified: n-isopropylpropranol; 1-(α-naphthoxy)-2,3-propanediol; cyclohydroxylated 1-(α-naphthoxy)-2,3-propanediol; α-naphthoxyacetic acid; α-naphthol; and 1,4-dihydroxynaphthyl.
Isopropylamine and hexadeuterated isopropylamine were identified as urinary metabolites of propranolol and hexadeuterated propranolol, respectively; this is believed to be the first recorded single-step oxidative deamination reaction of n-isopropylamine compounds.
An active metabolite, 4-hydroxypropranolol, is generated during initial oral treatment (rather than during intravenous or long-term oral treatment). The β-adrenergic blocking potency of 4-hydroxypropranolol is approximately the same as that of propranolol, and its plasma concentration is likely approximately equal to that of propranolol. This metabolite is eliminated more rapidly than propranolol, and is almost undetectable in plasma 6 hours after oral administration. One study indicated that the production of 4-hydroxypropranolol is not significant after intravenous or long-term oral administration, and its β-adrenergic blocking activity is more reflected in propranolol concentration. The ability of propranolol to hydroxylate into active metabolites may vary between individuals. Furthermore, some other metabolites of propranolol may have antiarrhythmic activity but do not possess β-adrenergic blocking activity. Propranolol is almost entirely metabolized in the liver, and at least eight metabolites have been identified in urine. Only 1-4% of the orally or intravenously administered drug appears in feces as the parent drug and its metabolites. Biological half-life: The half-life of propranolol at commonly used therapeutic doses is 3.4-6 hours with long-term use. Single-dose studies typically show shorter half-lives, of 2-3 hours.

Toxicity Summary
Identification: Propranolol is a class II antiarrhythmic drug, belonging to the β-adrenergic blocker family. Propranolol hydrochloride is a white, odorless crystalline powder. It is readily soluble in ethanol; slightly soluble in chloroform; and practically insoluble in ether. Cardiovascular Diseases: Propranolol is a non-selective β-blocker, primarily used to treat hypertension, angina pectoris, and to prevent re-infarction in patients with myocardial infarction. It is also used to control anxiety symptoms and to treat supraventricular tachycardia, hypertrophic obstructive cardiomyopathy, and myocardial infarction. Endocrine Disorders: Used to treat hyperthyroidism and thyroid storm; in combination with α-blockers for preoperative treatment of pheochromocytoma. Liver Diseases: Used to prevent portal hypertension bleeding. Nervous System Disorders: Propranolol has also been used to treat extrapyramidal disorders and prevent migraines. Anxiety Disorders: Propranolol can be used for acute stress reactions, somatic anxiety, and panic reactions, but its efficacy remains controversial. Human Exposure: Major Risks and Target Organs: Beta-blockers compete with endogenous and/or exogenous beta-adrenergic agonists. Propranolol is not cardiac selective and has no intrinsic sympathomimetic activity. It has membrane-stabilizing effects and is highly lipid-soluble. At toxic doses, propranolol exhibits significant negative chronotropic and inotropic effects, as well as quinidine-like cardiac effects. The cardiovascular system is its primary target organ. Propranolol can reduce sinus rate, atrioventricular conduction, intraventricular conduction, and myocardial contractility. Due to its high lipid solubility, central nervous system toxicity (coma and seizures) may also occur. Clinical Effects Overview: Toxicity usually occurs within 1 to 2 hours after ingestion, but the onset time may vary depending on the formulation. Symptoms may include: Cardiovascular disturbances: bradycardia, varying degrees of atrioventricular block, intraventricular block, hypotension, cardiogenic shock, and pulmonary edema. Neurological symptoms: coma and seizures. Respiratory depression and apnea. Cardiovascular failure and respiratory arrest may occur suddenly. Patients with underlying cardiovascular disease are more likely to experience adverse cardiac reactions to propranolol. Propranolol may induce bronchospasm in patients with asthma. Contraindications: Absolute contraindications: Asthma, congestive heart failure, atrioventricular block, bradycardia, and treatment with amiodarone. Relative contraindications: Raynaud's disease, diabetes. Routes of administration: Oral: Ingestion is the most common cause of poisoning. Inhalation: No cases of poisoning have been reported. Nasal administration of 10 mg propranolol has a rapid onset of action and is comparable to intravenous administration. Parenteral administration: No cases of overdose have been reported. Cardiovascular symptoms have been reported after therapeutic doses. Absorption: After oral administration, propranolol is almost completely and rapidly absorbed from the gastrointestinal tract. However, due to high first-pass metabolism and hepatic binding, its absolute bioavailability is only about 30%, and there is considerable individual variability. Peak plasma concentrations occur 1 to 2 hours after administration. After administration of sustained-release formulations, peak plasma concentrations occur 7 hours after absorption. Distribution: Approximately 90% to 95% of the drug is bound to plasma proteins. Propranolol is highly lipophilic: it can cross the blood-brain barrier and the placenta. Biological half-life determined by route of administration: After oral administration, the pharmacokinetics of propranolol are saturated. The plasma half-life is 3 to 6 hours, with the extended-release formulation having a half-life of approximately 12 hours. Systemic clearance is 800 mL/min/1.73 m². Overdose prolongs the plasma half-life. One study reported a half-life of 16 hours. In two reported cases, the half-lives were 13.8 hours and 8.3 hours, respectively. In five cases, the mean plasma half-life was 10.5 hours (range: 5.1 to 17 hours). Metabolism: Propranolol is primarily metabolized in the liver. At least one metabolite, 4-hydroxypropranolol, is biologically active. Hepatic metabolism is saturated, and bioavailability may increase with overdose. Elimination via exposure: Propranolol is completely eliminated within 48 hours after a single oral dose, primarily through hepatic metabolism. Less than 0.5% of the drug is excreted unchanged in the urine. Renal clearance is 12 mL/kg/min. Approximately 20% of the dose is excreted primarily as glucuronide conjugates in the urine. The concentration of propranolol in breast milk is approximately 50% of its blood concentration. Mechanism of action and toxicology: Propranolol is a non-selective β-blocker and does not possess intrinsic sympathomimetic effects. It has membrane-stabilizing effects and is highly lipid-soluble. At toxic doses, propranolol exhibits significant negative chronotropic and inotropic effects, as well as quinidine-like cardiac effects: leading to decreased heart rate, sinoatrial node and atrioventricular block, prolonged intraventricular conduction, and decreased cardiac output. β2-blockers may cause bronchospasm and hypoglycemia. Due to its high lipid solubility, propranolol can cross the blood-brain barrier and may cause coma and seizures. Pharmacodynamics: Beta-blockers compete with endogenous and/or exogenous beta-adrenergic agonists. Their specific action depends on their selectivity for β1 receptors (located in the heart) or β2 receptors (located in the bronchi, blood vessels, stomach, intestines, and uterus). Beta-blockers are classified according to their cardiac selectivity, membrane stabilizing effect, intrinsic sympathomimetic effect, and lipid solubility. At therapeutic doses, propranolol can slightly reduce heart rate (15%), supraventricular conduction, and cardiac output (15% to 20%). Cardiac work and oxygen consumption are also reduced. Propranolol can reduce renin secretion. Propranolol is available in racemic formulations: the dextrorotatory isomer primarily exerts beta-blocking effects, while the levorotatory isomer primarily exerts membrane stabilizing effects. Toxicity: Human Data: Adults: The toxicity of propranolol varies among individuals, which may be related to underlying heart disease, use of other cardiotoxic drugs, and differences in first-pass metabolism. Children: A 2-year-old child experienced drowsiness, second-degree atrioventricular block, and hypoglycemia after taking 70 mg. A 5-year-old child experienced drowsiness, delirium, and hallucinations after taking 100 mg. Drug Interactions: Decreased Bioavailability: Antacids reduce gastric absorption of propranolol. Barbiturates, phenytoin sodium, and rifampin can increase the first-pass clearance of propranolol by inducing hepatic enzymes. Increased Bioavailability: Histamine H2 receptor antagonists and oral contraceptives can reduce hepatic metabolism by inhibiting enzyme activity, increasing plasma propranolol concentrations by up to 50%. Reduced Efficacy: Nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the antihypertensive effect of propranolol. Nifedipine may exacerbate withdrawal symptoms of beta-blockers. Enhanced Efficacy: Digitalis, amiodarone, verapamil, and diltiazem can enhance the bradycardia induced by propranolol. Verapamil, preniramine, flecainide, and disopyramide can enhance the negative inotropic effect of propranolol. Major adverse reactions: Several adverse reactions have been reported during propranolol treatment. Cardiovascular system: sinus bradycardia, atrioventricular block, hypotension, worsening of left ventricular failure, cardiogenic shock, intermittent claudication. Respiratory system: bronchospasm, worsening of asthma symptoms in patients with known asthma, pulmonary edema. Central nervous system: depression, psychosis, seizures, hallucinations. Musculoskeletal system: muscle weakness, worsening of myasthenia gravis, peripheral neuropathy. Gastrointestinal system: vomiting, diarrhea, dry mouth. Endocrine and metabolic system: hypoglycemia, hyperkalemia, hypothyroidism, sexual dysfunction (impotence). Skin: urticaria, exfoliative dermatitis. Hematologic system: agranulocytosis (immune reaction), thrombocytopenia. Teratogenicity: There has been a report of a newborn developing tracheoesophageal fistula after a mother took propranolol during pregnancy. However, the teratogenic effects of propranolol have not been confirmed. Pregnancy: There have been reports of newborns born to mothers who took propranolol prenatally experiencing hypoglycemia and lethargy. Other: Propranolol treatment may exacerbate anaphylactic shock. Clinical Manifestations: Acute Poisoning: Ingestion: The severity of propranolol poisoning depends on its cardiotoxicity and the dose ingested, the presence of underlying heart disease, and the presence of other cardiotoxic drugs. Symptoms and signs appear within 1 to 2 hours and may include: Cardiovascular effects: bradycardia, hypotension, cardiogenic shock. ECG may show junctional rhythm, atrioventricular block, and widened QRS complex. Central nervous system effects: lethargy, coma, convulsions, and dilated pupils. Severe shock can lead to inadequate ventilation. Parenteral Exposure: Cardiovascular effects: bradycardia, hypotension, cardiogenic shock. ECG may show junctional rhythm, atrioventricular block, and widened QRS complex. Central nervous system symptoms include: lethargy, coma, convulsions, and dilated pupils. Severe shock can lead to inadequate ventilation. Course, Prognosis, and Causes of Death: Patients who survive 48 hours after acute poisoning or who have not experienced cardiac arrest before hospitalization usually recover. Death may be caused by cardiac arrest, manifested as hypoxemia. Prognosis depends on the ingested dose; patients with underlying heart disease or who have ingested other cardiotoxic drugs have a worse prognosis. Systemic Description of Clinical Manifestations: Cardiovascular System: Acute Phase: Cardiovascular symptoms are the main feature of propranolol poisoning. Bradycardia is the most common symptom (occurring in 60% to 90% of cases) and usually occurs shortly after ingestion. Hypotension occurs in approximately 50% to 70% of cases. Hypotension and shock are due to decreased cardiac output and vasodilation. Cardiac arrest may occur within 1 to 2 hours after ingestion. A 60-year-old man has been reported to have experienced cardiac arrest within 45 minutes of taking an overdose of propranolol. Symptomatic poisoning patients usually present with electrocardiographic changes: sinus or junctional bradycardia and atrioventricular block (first to third degree) are most common. QRS widening, bundle branch block, or QT prolongation are less common. Respiratory System: Acute: Respiratory depression and apnea are often associated with severe shock, caused by cerebral hypoxia. Pulmonary edema may occur, especially in patients with pre-existing cardiac dysfunction. Bronchospasm may occur in susceptible patients. Nervous System: Central Nervous System: Acute: Drowsiness, lethargy, agitation, delirium, hallucinations, and mydriasis may occur. Coma is usually only seen in patients with cardiovascular failure. Seizures have been reported after high doses. Seizures may be due to hypotension or the direct effects of propranolol (membrane stabilizing effect). Chronic: Fatigue, central nervous system depression, hallucinations, and psychosis have been reported. Autonomic Nervous System: Acute: Beta-blocker effect. Chronic: Beta-blocker effect. Skeletal and Smooth Muscles: Chronic: Muscle fatigue may occur. Gastrointestinal Tract: Acute: Vomiting and nausea may occur; two cases of lower esophageal sphincter spasm have been reported. There have been reports of mesenteric ischemia following propranolol overdose. Eyes, ears, nose, and throat: Local effects: Acute: Mydriasis and diplopia may occur. Metabolism: Acid-base imbalance: Metabolic acidosis may occur in severe poisoning with shock. Fluid and electrolyte disturbances: Low or high potassium levels have been reported in rare cases. Other: Two cases of hypoglycemia have been reported in children with poisoning.

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Use during pregnancy and lactation
◉ Overview of use during lactation
Because propranolol is present in low amounts in breast milk and infants ingest small quantities, no adverse effects are expected on breastfed infants. Lactation studies have not identified any adverse reactions in breastfed infants clearly attributable to propranolol. No special attention is required. Propranolol has been successfully used to treat persistent breast pain during lactation.
◉ Effects on Breastfed Infants
A study of mothers taking beta-blockers while breastfeeding found a numerically increased number of adverse events, but this was not statistically significant. Although the affected infants were age-matched to control groups, the age of the affected infants was not specified. Among eight mothers taking propranolol, one reported lethargy in her breastfed infant, but she was also taking other unspecified antihypertensive medications.
The French pharmacovigilance system reported a case of bradycardia in a 2-day-old breastfed infant. However, the report did not specify whether the mother had taken propranolol before delivery or whether the drug could have been passed to the infant through the placenta.
◉ Effects on Lactation and Breast Milk
As of the revision date, no published information was found regarding the effects of beta-blockers or propranolol during normal breastfeeding. A study of six patients with hyperprolactinemia and galactorrhea found no change in serum prolactin levels after β-adrenergic blockade with propranolol.
Drug Interactions
Propranolol can antagonize cardiac excitatory effects, which may limit the efficacy of hydralazine, and combination therapy has been shown to be more effective than either drug alone.
In two patients with thyrotoxicosis treated with high doses (120 mg/day for 14 days) of propranolol, the neuromuscular blocking effect induced by tubocurarine was prolonged. …In animal studies, decanamine and succinylcholine have been shown to interact with propranolol in a similar manner.
Propranolol can increase the acute central nervous system toxicity of ether, hexobarbital, morphine, and ethyl carbamate in mice.
Propranolol can block the cardiac excitatory effects of adrenaline. If epinephrine is used in patients taking propranolol, reflex tachycardia may occur, /SRP: a drop in blood pressure due to β-receptor blockade of blood vessels/. For more complete data on interactions of propranolol hydrochloride (16 in total), please visit the HSDB records 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-blockers; anxiolytics; antiarrhythmics; antihypertensives; sympathomimetic agents; vasodilators
/SRP: Previous Uses/: Propranolol has been shown to be effective in many cases when digitalis (whether or not in combination with quinidine and/or procainamide) fails to reduce ventricular rate; in addition, propranolol has been used to treat paroxysmal atrial tachycardia caused by digitalis poisoning.
Propranolol is also used to treat hypertrophic obstructive cardiomyopathy. In these diseases, strong contractions of the myocardium along the ventricular outflow tract can significantly increase outflow resistance, especially during exercise. …It is sometimes used to treat tachycardia and arrhythmias in patients with pheochromocytoma.
Drugs (Veterinary): …Atropine in combination with propranolol has been found to be effective in treating oleander poisoning.
For more complete data on the therapeutic uses of propranolol hydrochloride (25 in 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 used in combination with myocardial depressant anesthetics, tricyclic antidepressants, or oral hypoglycemic agents.
According to one report, 1% propranolol eye drops can cause severe pain lasting up to 15 minutes and induce…congestion and mild mydriasis may occur, but according to other researchers, most patients tolerated it well with up to 4 daily doses for 3-4 months, with burning sensation and conjunctival congestion occurring in only 8 out of 47 eyes.
Contraindicated in patients with cardiogenic shock, sinus bradycardia, first-degree or higher atrioventricular block, bronchial asthma, and congestive heart failure. Adverse reactions include fatigue, dizziness, depression, bradycardia, paresthesia in the hands, arterial insufficiency (e.g., Raynaud's syndrome), nausea, and diarrhea. Patients with bronchospasm should ideally avoid using this medication, and patients with diabetes must be closely monitored.
In some patients with angina treated with propranolol, the frequency, duration, and severity of angina attacks increased after abrupt discontinuation, usually occurring within 24 hours. These attacks were unstable and unresponsive to nitroglycerin. Acute and even fatal myocardial infarction and sudden death have also occurred in some patients receiving angina treatment after abrupt discontinuation of propranolol. In hypertensive patients, abrupt discontinuation of propranolol can produce a syndrome similar to acute thyrotoxicosis, characterized by tension, anxiety, tachycardia, and excessive sweating; these symptoms appear within one week of discontinuation and resolve upon restarting propranolol treatment.
For more complete data on drug warnings for propranolol hydrochloride (31 in total), please visit the HSDB record page.

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1. In isolated spontaneously beating rat atria, diltiazem (0.01 to 0.1 μM) shifted the atrial rate-concentration response curve of isoproterenol to the right in a non-parallel manner and reduced its peak value. Under the same experimental conditions, (+/-)-propranolol (0.03 to 0.1 μM) acted as a competitive β-adrenergic receptor antagonist. ² While (+/-)-propranolol (IC50 = 12 nM) and isoproterenol (IC50 = 0.9 μM) inhibited the binding of (-)-[3H]-dihydroalprolol to rat meningeal formulations, a inhibition not observed with diltiazem at concentrations up to 10 μM. ³ Diltiazem (rather than (+/-)-propranolol) antagonizes the positive chronotropic response of spontaneously beating rat atrial tachycardia to calcium. ⁴ Some studies suggest that diltiazem inhibits isoproterenol-induced tachycardia by affecting calcium ions, which may be a key regulator in a series of events linking β-adrenergic receptor 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.)