Atenolol

TENORMIN · (RS)-ATENOLOL · Seles · Aterol · Tenolol · ici66082 · dl-Atenolol · (RS)-4-[2-HYDROXY-3-[(1-METHYLETHYL)AMINO]PROPOXY]BENZENEACETAMIDE

https://huagongshe.com/de/chemical/2249

Identifikatoren & physikalische Daten

CAS No.	29122-68-7
Summenformel	C14H22N2O3
Durchschnittliche Molmasse	266,34 g/mol
Monoisotopische Masse	266,16304257 g/mol
SMILES	CC(C)NCC(O)COc1ccc(CC(N)=O)cc1
InChIKey	METKIMKYRPQLGS-UHFFFAOYSA-N
PubChem CID	2249
ChEMBL	CHEMBL24
ChEBI	CHEBI:2904
EC No.	249-451-7
DTXSID	DTXSID2022628
Lokaler Name	Atenolol

Chemische & physikalische Eigenschaften

XLogP	0,2
Polarare Oberfläche (TPSA)	84,6
H-Brücken-Donoren	3
H-Brücken-Akzeptoren	4
Frei drehbare Bindungen	8
Schwere Atome	19
Formalladung	0
Komplexität	263
LogP (Verteilungskoeffizient)	0.16log Kow= 0.16
Color/Form	White, crystalline powderCrystals from ethyl acetateColorless crystals
Löslichkeit	13300Freely soluble in methanolsoluble in acetic acid, DMSOsparingly soluble in 96% ethanolslightly soluble in isopropanolvery slightly soluble in acetone, dioxanepractically insoluble in acetonitrile, ethyl acetatechloroformFreely soluble in 1 N HCl (300 mg/ml @ 25 °C)less soluble in chloroform (3 mg/ml @ 25 °C)In water, 1.33X10+4 mg/l @ 25 °C13.3 mg/mL at 25 °C>40 [ug/mL] (The mean of the results at pH 7.4)H2O: 0.3 mg/mL13.5mg/L(25 ºC)
Schmelzpunkt	158-160146 - 148 °C147 °C154°C
Caco2 Permeability	-6.44
Physical Description	Solid
Ionization Efficiency	Positive4.952.7Agilent XCTElectrospray ionizationformic acid (5.3nM)
Dissociation Constants	9.589.549.6pKa = 9.6
Collision Cross Section	157.8 Å² [M+H]+ [CCS Type: DTBuffer gas: N2Ionization: ESI+Dataset: TOXCASTSource Identifier: DTXSID2022628]157.9 Å² [M+H]+ [CCS Type: DTIonization: APCI+164.2 Å² [M+Na]+ [CCS Type: DT155.32 Å² [M+H-H2O]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]158.38 Å² [M+H]+ [CCS Type: TW165.83 Å² [M+K]+ [CCS Type: TW163.26 Å² [M+Na]+ [CCS Type: TW159.5 Å² [M+H]+ [CCS Type: TWMethod: Major Mix IMS/Tof Calibration Kit (Waters)]159 Å² [M+H]+ [CCS Type: TW
Other Experimental Properties	Dipole moment 5.71 D @ 20 °C in propionic acid
Siedepunkt	409.54°C (rough estimate)
Dichte	1.0807 (rough estimate)
Brechungsindex	1.5110 (estimate)
Flammpunkt	2℃
Lagerbedingungen	2-8°C
Aggregatzustand	powder
pKa (Säurekonstante)	9.6(at 25℃)
Farbe	white to off-white
Merck	14,859
BCS Class	3
InChI	1S/C14H22N2O3/c1-10(2)16-8-12(17)9-19-13-5-3-11(4-6-13)7-14(15)18/h3-6,10,12,16-17H,7-9H2,1-2H3,(H2,15,18)
InChIKey	METKIMKYRPQLGS-UHFFFAOYSA-N
SMILES	N(C(C)C)CC(O)COc1ccc(cc1)CC(=O)N
CAS Datenbank	29122-68-7(CAS DataBase Reference)
NIST chemische Informationen	Atenolol(29122-68-7)
EPA chemische Informationen	Benzeneacetamide, 4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]- (29122-68-7)

Sicherheit & Vorschriften

GHS-Einstufung	This chemical does not meet GHS hazard criteria for 3.4% (3 of 89) of reports.WarningH302 (79.8%): Harmful if swallowed [Warning Acute toxicity, oral]H319 (67.4%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]H351 (64%): Suspected of causing cancer [Warning Carcinogenicity]H362 (74.2%): May cause harm to breast-fed children [Reproductive toxicity, effects on or via lactation]P203, P260, P263, P264, P264+P265, P270, P280, P301+P317, P305+P351+P338, P318, P330, P337+P317, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 89 reports by companies from 24 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.Reported as not meeting GHS hazard criteria per 3 of 89 reports by companies.There are 22 notifications provided by 86 of 89 reports by companies with hazard statement code(s).Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.
Regulatorische Informationen	Hazard Traits - Developmental ToxicityAuthoritative List - Prop 65Report - regardless of intended function of ingredient in the productAtenolol: Does not have an individual approval but may be used under an appropriate group standard
Weitere Sicherheitsinformationen	IMAP assessments - Benzeneacetamide, 4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]-: Human health tier I assessmentIMAP assessments - Benzeneacetamide, 4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]-: Environment tier I assessment
FDA-Anforderungen	Atenolol, used as a beta adrenergic blocking agent, was approved by FDA for marketing in the United States 8/81.The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed drug products, incl atenolol, approved on the basis of safety and effectiveness by FDA under sections 505 and 507 of the Federal Food, Drug, and Cosmetic Act.Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended21 U.S.C. 321-392).
Hazard Classes and Categories	Acute Tox. 4 (79.8%)Eye Irrit. 2 (67.4%)Carc. 2 (64%)Lact. (74.2%)Repr. 1A (100%)Lact. (100%)Aquatic Chronic 2 (100%)
Lagerbedingungen	Atenolol tablets ... should be protected from heat, light, and moisture and stored in well closed, light-resistent containers at 20-30 °C. Atenolol injection should be stored at room temperature between 20-25 °C and protected from light.
Entsorgungsverfahren	SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air qualitypotential migration in soil or watereffects on animal, aquatic, and plant lifeand conformance with environmental and public health regulations.
Wechselwirkungen	Concomitant administration of atenolol with reserpine may increase the incidence of hypotension and bradycardia as compared with atenolol alone, because of reserpine's catecholamine-depleting activity. Atenolol also is additive with and may potentiate the hypotensive actions of other hypotensive agents (e.g., hydralazine, methylodpa).It has been shown that paradoxical pressor response to a beta adrenoceptor antagonist occurs in conscious rats pretreated with an alpha adrenoceptor antagonist. This study examines the influence of anaesthetic agents on mean arterial pressure response to a beta blocker. ... IV injections of all three beta blockers caused dose dependent increases in mean arterial pressure in urethane anesthetized rats. In halothane anesthetized rats, propranolol and atenolol did not alter mean arterial pressure ... In the presence of pentobarbitone, none of the beta blockers raised mean arterial pressure. ... /When/ propranolol or atenolol were iv injected in pentobarbitone anesthetized rats treated with both phentolamine and adrenaline, /they both/ ... raised the mean arterial pressure. /These/ results show that anesthetic agents differentially affect the mean arterial pressure response to a beta blocker.In a recent study in which metabolic characteristics of newly detected obese and nonobese hypertensive subjects were compared with those of normotensive subjects, insulin sensitivity was decreased, fasting insulin values and insulin values after an intravenous glucose tolerance test were increased, and fasting and intravenous glucose tolerance glucose values were increased in both hypertensive groups. ... The effects of various antihypertensive agents on these metabolic variables have been assessed in prospective trials. Treatment with the beta 1 selective blocking agents metoprolol and atenolol was associated with decreased insulin sensitivity and increased fasting values of insulin and glucose.A double blind, randomized, crossover study of the pharmacokinetics of nifedipine and atenolol was conducted in 15 healthy male subjects (mean age 32 yr) who received a single oral tablet containing 50 mg atenolol, a sustained action tablet containing 20 mg nifedipine, both the atenolol and nifedipine tablets together, or an oral capsule containing 50 mg atenolol and 20 mg sustained release nifedipine. There was no difference between atenolol alone, given with nifedipine tablet or in the combination tablet with respect to time to maximum blood concentration or elimination half-life. ... /In conclusion,/ the fixed combination of nifedipine and atenolol is bioequivalent to the free combination and the bioavailability of both drugs in the fixed combination is equivalent to that of the single tablets.For more Interactions (Complete) data for ATENOLOL (14 total), please visit the HSDB record page.
Hepatotoxicity	Atenolol therapy has been associated with mild-to-moderate elevations of serum aminotransferase levels in 1% to 2% of patients. These elevations, however, are usually asymptomatic and transient and resolve even with continuation of therapy. A few instances of clinically apparent, acute liver injury attributable to atenolol have been reported. In view of its wide scale use, atenolol induced liver injury is exceedingly rare. The onset of injury has been within 1 to 4 weeks and pattern of liver enzyme elevations has been hepatocellular or mixed. Symptoms of hypersensitivity (rash, fever, eosinophilia) are uncommon as is autoantibody formation. Most cases are self-limiting and resolve rapidly once atenolol is stoppedhowever, at least one fatal instance has been reported.Likelihood score: D (Possible rare cause of clinically apparent liver injury).
Unerwünschte Wirkungen	According to product labeling, the adverse effects of atenolol are listed below.* Common adverse effects include bradycardia, diarrhea, dizziness, constipation, confusion, dyspnea, headache, heart failure, erectile dysfunction, nausea, fatigue, paraesthesia, peripheral coldness, rash, sleep disorders, syncope, visual impairment, and bronchospasm.* Rare adverse effects include alopecia, dry mouth, postural hypotension, psychosis, psoriasis, thrombocytopenia, depression, mild transaminitis, and depression.* The BRASH syndrome is characterized by severe bradycardia, renal failure, atrioventricular blockade, shock, and hyperkalemia. If suspicion of BRASH syndrome exists, discontinuation of atenolol is recommended.Drug-Drug Interactions* Caution is advised when using rivastigmine concurrently with β-blockers such as atenolol, especially in patients with sick sinus syndrome or cardiovascular comorbidities due to the risk of syncope and bradycardia.* Administering atenolol concurrently with amiodarone, digoxin, or verapamil may cause heart block, bradycardia, and left ventricular dysfunction.* Antipsychotics and β-blockers have the potential for interactions. A case report documenting bradycardia induced by the combination of risperidone and atenolol has been published.* As amifostine can cause a rapid drop in blood pressure, it is advisable to avoid concurrently using blood pressure–lowering agents, including atenolol, with amifostine.* As the American Academy of Family Physicians (AAFP) guidelines recommend, β-blockers, such as atenolol, should be tapered and discontinued several days before discontinuing clonidine to reduce the risk of rebound hypertension.
Expositionspfade	Approximately 50% of an oral dose is absorbed from the gastrointestinal tract, the remainder being excreted unchanged in the feces.
Milk Concentrations	Atenolol is distributed into milk. The drug distributes into milk in concentrations 1.5-6.8 times those in maternal serum. In addition, adverse beta-adrenergic effects (eg, bradycardia) and potentially toxic serum atenolol concentrations (2 ug/ml 48 hours after discontinuance of breast feeding in at least one infant) can occur.
Toxizitätsübersicht	Signs and Symptoms of OverdoseSymptoms of atenolol toxicity may include bradycardia, lethargy, hypotension, respiratory drive disorders, hypothermia, hypoglycemia, and seizures.Management of OverdoseThe treatment for β-blocker toxicity is primarily supportive. If administered orally, any unabsorbed drug can be removed by gastric lavage or activated charcoal (within 1 to 2 hours). Hemodialysis is effective in eliminating atenolol from the general systemic circulation. Inotropes and chronotropes, such as IV epinephrine and atropine, are recommended for treating severe bradycardia. Usually, atropine is administered as a 0.5-mg IV or intraosseous bolus and may be repeated every 3 to 5 minutes, up to a total dose of 3 mg. A transvenous cardiac pacemaker may also be utilized in refractory cases or for treating second- or third-degree heart block.A titrated glucagon bolus at a dose of 50 mcg/kg can improve myocardial contractility and atrioventricular conduction and increase heart rate in patients. Continuous blood pressure monitoring is imperative, and vasopressors such as norepinephrine (levarterenol) may be considered in hypotension. A β-2 agonist such as aminophylline or isoproterenol may alleviate symptoms for patients with bronchospasm. In cases refractory to the standard treatment, high-dose insulin euglycemic therapy, initiated with a 1 unit/kg bolus followed by a 1 unit/kg/h drip, may be considered to manage overdose under the guidance of a toxicologist.Lignocaine can be used in the management of arrhythmias resulting from β-blocker toxicity. Veno-arterial extracorporeal membrane oxygenation is also associated with reduced mortality. For asymptomatic β-1-blocker overdoses, monitoring the patient for at least 6 hours is recommended.Like metoprolol, atenolol competes with sympathomimetic neurotransmitters such as catecholamines for binding at beta(1)-adrenergic receptors in the heart and vascular smooth muscle, inhibiting sympathetic stimulation. This results in a reduction in resting heart rate, cardiac output, systolic and diastolic blood pressure, and reflex orthostatic hypotension. Higher doses of atenolol also competitively block beta(2)-adrenergic responses in the bronchial and vascular smooth muscles.
Signs and Symptoms	Symptoms of an atenolol overdose include a slow heart beat, shortness of breath, fainting, dizziness, weakness, confusion, nausea, and vomiting.
Human Toxicity Excerpts	/HUMAN EXPOSURE STUDIES/ A case of severe bradycardia, hypotension and marked hyperglycemia in a 15 yr old girl who ingested 10 oral tablets of 50 mg atenolol in a suicide attempt is reported. The patient was treated with gastric lavage and activated charcoal 60 gno tablets were recovered in the lavage fluid. After an iv infusion of 5% dextrose was started, the patient's blood glucose increased to 90 mg/dl. She was given atropine sulfate 0.5 mg iv for hemodynamic support. It was concluded that, because of the severe and prolonged toxicity in this patient after a minimal overdose, caution is warranted in dealing with atenolol overdose./HUMAN EXPOSURE STUDIES/ To compare the effects of uteroplacental circulation of two beta adrenoceptor blockers, atenolol (cardioselective) and pindolol (non-selective with intrinsic sympathomimetic activity). Design: Controlled double blind double dummy study, ...29 women with pregnancy induced hypertension in the third trimester /were/ randomized to atenolol /13/ and to pindolol /16/. ...Pulsatility index in fetal aorta, umbilical artery, and maternal arcuate artery, volumetric blood flow in fetal aorta and umbilical vein /were measured/. /The/ mean arterial blood pressure decreased by 9.0 (95% confidence interval -13.0 to -5.0) mm Hg in the atenolol group and by 7.8 (-11.4 to -4.2) mm Hg in the pindolol group. During atenolol treatment the pulsatility index increased significantly from 1.82 (standard deviation 0.20) to 2.07 (0.32) in the fetal thoracic descending aorta, from 1.44 (0.28) to 1.79 (0.27) in the abdominal aorta, and from 0.93 (0.17) to 1.05 (0.19) in the umbilical arterythe volumetric blood flow in the umbilical vein decreased from 106 (28.8) to 84 (22.6) ml/min/kg. No such changes were seen after treatment with pindolol. Birth weight was similar in the two groups but placental weight was significantly different 529 (122) g in atenolol group v 653 (136) g in pindolol groupp=0.03). /In conclusion,/ the hypotensive effect was similar with both drugs, but only the beta 1-blocker atenolol had significant effects on fetal hemodynamics, although within normal ranges. The implications of these findings can be only speculative, but negative fetal consequences of beta 1-adrenoceptor blockade cannot be excluded./HUMAN EXPOSURE STUDIES/ To compare the obstetric and fetal outcome between women receiving atenolol (as monotherapy) and other antihypertensive drug monotherapies, and also to investigate the effect of duration of treatment on fetal growth, we performed a retrospective cohort study of 312 pregnancies in 223 women ... Atenolol (as monotherapy) was given in 78 pregnancies (25.0%), other types of antihypertensive drugs as monotherapy were given in 53 pregnancies (17.0%), and multiple drug combinations were given in 90 pregnancies (28.8%). In 91 pregnancies (29.2%) no antihypertensive drugs were given. Atenolol was found to be associated with lower birth weight and ponderal index values, with a trend toward a higher prevalence of preterm (<37 weeks) delivery and small-for-gestational-age babies when compared to other antihypertensive drugs as monotherapy, or to no treatment.
Carcinogen Classification	No indication of carcinogenicity to humans (not listed by IARC).
Drug Induced Liver Injury	Drug Induced Liver Injury Rank (DILIrank 2.0)AtenololvLess-DILI-concern4Adverse reactionsDOI:10.1016/j.drudis.2016.02.015
Non-Human Toxicity Excerpts	/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Chronic studies employing oral atenolol performed in animals have revealed the occurrence of vacuolation of epithelial cells of Brunner's glands in the duodenum of both male and female dogs at all tested dose levels of atenolol (starting at 15 mg/kg/day...) and increased incidence of atrial degeneration of hearts of male rats at 300 but not 150 mg atenolol/kg/day./LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ No evidence of carcinogenicity was observed following administration of atenolol at dosages up to 300 mg/kg daily... for 18 months in mice or 18 or 24 months in rats. However, an increased of benign adrenal medullary tumors in males and females, mammary fibroadenomas in females, and anterior pituitary adenomas and thyroid parafollicular cell carcinomas in males was observed at 24 months in rats receiving 500-1,500 mg/kg of atenolol daily./LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Reproduction studies in male and female rats using atenolol dosages up to 200 mg/kg daily... have not revealed evidence of impaired fertility./LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Atenolol has been shown to produce a dose-related increase in embryo/fetal resorptions in rats at doses equal to or greater than 50 mg/kg/day... Although similar effects were not seen in rabbits, the compound was not evaluated in rabbits at doses above 25 mg/kg/day ...For more Non-Human Toxicity Excerpts (Complete) data for ATENOLOL (6 total), please visit the HSDB record page.
Antidote and Emergency Treatment	Emergency and supportive measures. 1. Maintain an open airway and assist ventilation if necessary. 2. Treat coma, seizures, hypotension, hyperkalemia, and hypoglycemia if they occur. 3. Treat bradycardia with atropine, ... IVisoproterenol ...or cardiac pacing. 4. Treat bronchospasm with nebulized bronchodilators. 5. Continuously monitor the vital signs and ECG for at least 6 hours after ingestion. /Beta-adrenergic blockers/Specific drugs and antidotes. 1. Bradycardia and hypotension resistant to... /normal/ measures should be treated with glucagon, ... . Epinephrine (intravenous) infusion ... and titrating to effect. 2. Wide complex conduction defects caused by membrane-depressant poisoning may respond to sodium bicarbonate, ... as given for tricyclic antidepressant overdose. 3. Torsades de pointes polymorphous ventricular tachycardia associated with QT prolongation resulting from sotalol poisoning can be treated with isoproterenol infusion, magnesium, or overdrive pacing. Correction of hypokalemia may also be useful. /Beta-adrenergic blockers/Decontamination. 1. Prehospital. Administer activated charcoal if available. 2. Hospital. Administer activated charcoal. Consider gastric lavage for large ingestions, especially involving propranolol. Gastric emptying is not necessary for small ingestions if activated charcoal can be given promptly. /Beta-adrenergic blockers/Enhanced elimination. Most beta blockers, especially the more toxic drugs such as propranolol, are highly lipophilic and have a large volume of distribution (Vd). For those with a relatively small volume of distribution coupled with a long half-life or low intrinsic clearance (eg, acebutolol, atenolol, nadolol, or sotalol), hemoperfusion, hemodialysis, or repeat-dose charcoal may be effective. /Beta-adrenergic blockers/For more Antidote and Emergency Treatment (Complete) data for ATENOLOL (6 total), please visit the HSDB record page.
Wassergefährdungsklasse (WGK)	2
UN-Transportnummer	UN 1648 3 / PGII
Zollcode	29242995
RTECS-Nr.	AC3600000
R-Sätze (R)	22-36/37/38-20/21/22-36-11
Toxizität	LD50 in mice, rats (mg/kg): 2000, 3000 orally98.7, 59.24 i.v. (Fitzgerald)
Gefahrensymbole	Xn,F
Sicherheitshinweise (S)	22-24/25-36-26-36/37-16
Gefahrenklasse	IRRITANT
Lagerklasse	11 - Combustible Solids
Gefahrstoffdaten	29122-68-7(Hazardous Substances Data)

Anwendungen & Verwendung

Verwenden

Atenolol is 2-[4′[2-hydroxy-3-(iso-propylamino)propoxy]phenyl]acetamide (12.1.7) [11–13].Atenolol is a selective β1-adrenoblocker, or in other words, a cardioblocker. Like acebutol, atenolol possesses antianginal, antihypotensive, and antiarrhythmic action. It is used for arterial hypotension, preventing attacks of angina, sinus tachycardia, and preventing supraventricular tachyarrhythmia.