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Identification
NameLabetalol
Accession NumberDB00598  (APRD01062)
Typesmall molecule
Groupsapproved
Description

Blocker of both alpha- and beta-adrenergic receptors that is used as an antihypertensive. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
LabetalolumLatinINN
LabetololNot AvailableNot Available
Salts
Name/CAS Structure Properties
Labetalol Hydrochloride
Thumb
  • InChI Key: WQVZLXWQESQGIF-UHFFFAOYNA-N
  • Monoisotopic Mass: 364.155370383
  • Average Mass: 364.866
DBSALT000320
Brand names
NameCompany
AlbetolLeiras
LatolStandard
NormadateGlaxoSmithKline
NormodyneSchering
TrandateGlaxoSmithKline
Brand mixturesNot Available
Categories
CAS number36894-69-6
WeightAverage: 328.4055
Monoisotopic: 328.178692644
Chemical FormulaC19H24N2O3
InChI KeySGUAFYQXFOLMHL-UHFFFAOYSA-N
InChI
InChI=1S/C19H24N2O3/c1-13(7-8-14-5-3-2-4-6-14)21-12-18(23)15-9-10-17(22)16(11-15)19(20)24/h2-6,9-11,13,18,21-23H,7-8,12H2,1H3,(H2,20,24)
IUPAC Name
2-hydroxy-5-{1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl}benzamide
SMILES
CC(CCC1=CC=CC=C1)NCC(O)C1=CC(C(N)=O)=C(O)C=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassPhenylpropylamines
Direct parentPhenylpropylamines
Alternative parentsSalicylamides; Benzamides; Benzoyl Derivatives; Phenols and Derivatives; Polyols; Primary Carboxylic Acid Amides; Secondary Alcohols; 1,2-Aminoalcohols; Dialkylamines; Carboxylic Acids; Enolates; Polyamines; Enols
Substituentsbenzoyl; phenol derivative; 1,2-aminoalcohol; primary carboxylic acid amide; polyol; carboxamide group; secondary alcohol; enolate; secondary amine; secondary aliphatic amine; polyamine; carboxylic acid derivative; enol; carboxylic acid; amine; alcohol; organonitrogen compound
Classification descriptionThis compound belongs to the phenylpropylamines. These are compounds containing a phenylpropylamine moiety, which consists of a phenyl group substituted at the third carbon by an propan-1-amine.
Pharmacology
IndicationFor the management of hypertension (alone or in combination with other classes of antihypertensive agents), as well as chronic stable angina pectoris and sympathetic overactivity syndrome associated with severe tetanus. Labetalol is used parenterally for immediate reduction in blood pressure in severe hypertension or in hypertensive crises when considered an emergency, for the control of blood pressure in patients with pheochromocytoma and pregnant women with preeclampsia, and to produce controlled hypotension during anesthesia to reduce bleeding resulting from surgical procedures.
PharmacodynamicsLabetalol is an selective alpha-1 and non-selective beta adrenergic blocker used to treat high blood pressure. It works by blocking these adrenergic receptors, which slows sinus heart rate, decreases peripheral vascular resistance, and decreases cardiac output. Labetalol has two asymmetric centers and therefore, exists as a molecular complex of two diastereoisomeric pairs. Dilevalol, the R,R' stereoisomer, makes up 25% of racemic labetalol.
Mechanism of actionLabetalol HCl combines both selective, competitive, alpha-1-adrenergic blocking and nonselective, competitive, beta-adrenergic blocking activity in a single substance. In man, the ratios of alpha- to beta- blockade have been estimated to be approximately 1:3 and 1:7 following oral and intravenous (IV) administration, respectively. The principal physiologic action of labetalol is to competitively block adrenergic stimulation of β-receptors within the myocardium (β1-receptors) and within bronchial and vascular smooth muscle (β2-receptors), and α1-receptors within vascular smooth muscle. This causes a decrease in systemic arterial blood pressure and systemic vascular resistance without a substantial reduction in resting heart rate, cardiac output, or stroke volume, apparently because of its combined α- and β-adrenergic blocking activity.
AbsorptionCompletely absorbed (100%) from the gastrointestinal tract with peak plasma levels occurring 1 to 2 hours after oral administration. The absolute bioavailability of labetalol is increased when administered with food.
Volume of distributionNot Available
Protein binding50%
Metabolism

Primarily hepatic, undergoes significant first pass metabolism

Route of eliminationThese metabolites are present in plasma and are excreted in the urine, and via the bile, into the feces.
Half life6-8 hours
ClearanceNot Available
ToxicityLD50 = 66 mg/kg (Rat, IV). Side effects or adverse reactions include dizziness when standing up, very low blood pressure, severely slow heartbeat, weakness, diminished sexual function, fatigue
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Labetalol Action PathwayDrug actionSMP00368
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9943
Blood Brain Barrier - 0.8313
Caco-2 permeable + 0.8867
P-glycoprotein substrate Substrate 0.7073
P-glycoprotein inhibitor I Non-inhibitor 0.8908
P-glycoprotein inhibitor II Non-inhibitor 0.9269
Renal organic cation transporter Non-inhibitor 0.8457
CYP450 2C9 substrate Non-substrate 0.7448
CYP450 2D6 substrate Substrate 0.8918
CYP450 3A4 substrate Non-substrate 0.6202
CYP450 1A2 substrate Non-inhibitor 0.9046
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Inhibitor 0.8932
CYP450 2C19 substrate Inhibitor 0.8995
CYP450 3A4 substrate Non-inhibitor 0.8256
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8383
Ames test Non AMES toxic 0.9133
Carcinogenicity Non-carcinogens 0.9189
Biodegradation Not ready biodegradable 0.945
Rat acute toxicity 2.1174 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9501
hERG inhibition (predictor II) Non-inhibitor 0.7398
Pharmacoeconomics
Manufacturers
  • Apothecon inc div bristol myers squibb
  • Bedford laboratories div ben venue laboratories inc
  • Claris lifesciences ltd
  • Hospira inc
  • Taylor pharmaceuticals
  • Sagent strides llc
  • Schering corp sub schering plough corp
  • Prometheus laboratories inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mutual pharmaceutical co inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
Packagers
Dosage forms
FormRouteStrength
LiquidIntravenous
TabletOral
Prices
Unit descriptionCostUnit
Labetalol Hydrochloride 5 mg/ml1.36USDml
Trandate 300 mg tablet1.28USDtablet
Trandate 5 mg/ml vial1.25USDml
Trandate 200 mg tablet1.08USDtablet
Labetalol hcl 300 mg tablet1.02USDtablet
Normodyne 200 mg tablet1.0USDtablet
Labetalol hcl 200 mg tablet0.76USDtablet
Trandate 100 mg tablet0.68USDtablet
Labetalol hcl 100 mg tablet0.53USDtablet
Trandate 200 mg Tablet0.47USDtablet
Trandate 100 mg Tablet0.27USDtablet
Labetalol hcl 5 mg/ml vial0.1USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point188 °CU.S. Patent 4,012,444.
water solubility117 mg/L (at 25 °C)MCFARLAND,JW ET AL. (2001)
logP3.09HANSCH,C ET AL. (1995)
Caco2 permeability-5.03ADME Research, USCD
Predicted Properties
PropertyValueSource
water solubility5.78e-03 g/lALOGPS
logP1.73ALOGPS
logP1.89ChemAxon
logS-4.8ALOGPS
pKa (strongest acidic)8.05ChemAxon
pKa (strongest basic)9.8ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count4ChemAxon
polar surface area95.58ChemAxon
rotatable bond count8ChemAxon
refractivity94.72ChemAxon
polarizability36.83ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

U.S. Patent 4,012,444.

General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC07063
PubChem Compound3869
PubChem Substance46505511
ChemSpider3734
BindingDB25758
ChEBI6343
ChEMBLCHEMBL429
Therapeutic Targets DatabaseDAP000038
PharmGKBPA164743150
Drug Product Database2243539
RxListhttp://www.rxlist.com/cgi/generic2/labet.htm
Drugs.comhttp://www.drugs.com/cdi/labetalol.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/nor1301.shtml
WikipediaLabetalol
ATC CodesC07AG01
AHFS Codes
  • 24:24.00
PDB EntriesNot Available
FDA labelshow(401 KB)
MSDSshow(53.7 KB)
Interactions
Drug Interactions
Drug
AcetohexamideThe beta-blocker, labetalol, may decrease symptoms of hypoglycemia.
ChlorpropamideThe beta-blocker, labetalol, may decrease symptoms of hypoglycemia.
CimetidineCimetidine may increase the serum concentration of labetolol by decreasing its metabolism.
ClonidineIncreased hypertension when clonidine stopped
DihydroergotamineIschemia with risk of gangrene
DisopyramideThe beta-blocker, labetolol, may increase the toxicity of disopyramide.
EnfluraneMonitor arterial pressure closely
EpinephrineHypertension, then bradycardia
ErgonovineIschemia with risk of gangrene
ErgotamineIschemia with risk of gangrene
FenoterolAntagonism
FormoterolAntagonism
GliclazideThe beta-blocker, labetalol, may decrease symptoms of hypoglycemia.
GlipizideThe beta-blocker, labetalol, may decrease symptoms of hypoglycemia.
GlisoxepideThe beta-blocker, labetalol, may decrease symptoms of hypoglycemia.
GlyburideThe beta-blocker, labetalol, may decrease symptoms of hypoglycemia.
GlycodiazineThe beta-blocker, labetalol, may decrease symptoms of hypoglycemia.
HalothaneMonitor arterial pressure closely
IbuprofenRisk of inhibition of renal prostaglandins
IndomethacinRisk of inhibition of renal prostaglandins
Insulin GlargineThe beta-blocker, labetolol, may decrease symptoms of hypoglycemia.
IobenguaneMay diminish the therapeutic effect and increase chances of producing a false negative imaging result of Iobenguane as it depletes or inhibit reuptake of noradrenaline stores
IsofluraneMonitor arterial pressure closely
IsoprenalineAntagonism
LidocaineThe beta-blocker, labetalol, may increase the effect and toxicity of lidocaine.
MethysergideIschemia with risk of gangrene
OrciprenalineAntagonism
PipobromanAntagonism
PirbuterolAntagonism
PiroxicamRisk of inhibition of renal prostaglandins
PrazosinRisk of hypotension at the beginning of therapy
ProcaterolAntagonism
RepaglinideThe beta-blocker, labetalol, may decrease symptoms of hypoglycemia.
SalbutamolAntagonism
SalmeterolAntagonism
TerazosinIncreased risk of hypotension. Initiate concomitant therapy cautiously.
TerbutalineAntagonism
TolazamideThe beta-blocker, labetalol, may decrease symptoms of hypoglycemia.
TolbutamideThe beta-blocker, labetalol, may decrease symptoms of hypoglycemia.
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
VerapamilIncreased effect of both drugs
Food Interactions
  • Take without regard to meals.

Targets

1. Beta-1 adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Beta-1 adrenergic receptor P08588 Details

References:

  1. Riva E, Mennini T, Latini R: The alpha- and beta-adrenoceptor blocking activities of labetalol and its RR-SR (50:50) stereoisomers. Br J Pharmacol. 1991 Dec;104(4):823-8. Pubmed
  2. Monopoli A, Bamonte F, Forlani A, Ongini E, Parravicini L: Effects of the R, R-isomer of labetalol, SCH 19927, in isolated tissues and in spontaneously hypertensive rats during a repeated treatment. Arch Int Pharmacodyn Ther. 1984 Dec;272(2):256-63. Pubmed
  3. Sassard J, Zech PY, Pozet N, Cuisinaud G, Vincent M: [Comparative effects of an alpha 1 and beta 1-2 blocker (labetalol) and a beta-1 blocker (atenolol) in the hypertensive patient] J Pharmacol. 1983;14 Suppl 2:121-9. Pubmed
  4. Nakagawa Y, Takeda K, Sakurai H, Mitomi A, Imai S: [Antihypertensive effects of labetalol in three types of hypertensive models of rats (author’s transl)] Nippon Yakurigaku Zasshi. 1981 Apr;77(4):435-45. Pubmed
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  6. Pujos E, Cren-Olive C, Paisse O, Flament-Waton MM, Grenier-Loustalot MF: Comparison of the analysis of beta-blockers by different techniques. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Dec 1;877(31):4007-14. Epub 2009 Oct 17. Pubmed
  7. Rosendorff C: Beta-blocking agents with vasodilator activity. J Hypertens Suppl. 1993 Jun;11(4):S37-40. Pubmed
  8. van Zwieten PA: An overview of the pharmacodynamic properties and therapeutic potential of combined alpha- and beta-adrenoceptor antagonists. Drugs. 1993 Apr;45(4):509-17. Pubmed

2. Beta-2 adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Beta-2 adrenergic receptor P07550 Details

References:

  1. Doggrell SA: The effects of labetalol and dilevalol on isolated cardiovascular preparations of the guinea-pig and rat. J Pharm Pharmacol. 1992 Dec;44(12):1001-6. Pubmed
  2. Doggrell SA: Relaxant and beta 2-adrenoceptor blocking activities of labetalol, dilevalol, amosulalol and KF-4317 on the rat isolated aorta. J Pharm Pharmacol. 1988 Nov;40(11):812-5. Pubmed
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  4. Sassard J, Zech PY, Pozet N, Cuisinaud G, Vincent M: [Comparative effects of an alpha 1 and beta 1-2 blocker (labetalol) and a beta-1 blocker (atenolol) in the hypertensive patient] J Pharmacol. 1983;14 Suppl 2:121-9. Pubmed
  5. Pujos E, Cren-Olive C, Paisse O, Flament-Waton MM, Grenier-Loustalot MF: Comparison of the analysis of beta-blockers by different techniques. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Dec 1;877(31):4007-14. Epub 2009 Oct 17. Pubmed
  6. Rosendorff C: Beta-blocking agents with vasodilator activity. J Hypertens Suppl. 1993 Jun;11(4):S37-40. Pubmed
  7. van Zwieten PA: An overview of the pharmacodynamic properties and therapeutic potential of combined alpha- and beta-adrenoceptor antagonists. Drugs. 1993 Apr;45(4):509-17. Pubmed

3. Alpha-1 adrenergic receptor

Kind: protein group

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Alpha-1A adrenergic receptor P35348 Details
Alpha-1B adrenergic receptor P35368 Details
Alpha-1D adrenergic receptor P25100 Details

References:

  1. Bernstein JS, Ebert TJ, Stowe DF, Schmeling WT, Nelson MA, Woods MP: Partial attenuation of hemodynamic responses to rapid sequence induction and intubation with labetalol. J Clin Anesth. 1989;1(6):444-51. Pubmed
  2. Nakamura T, Maruyama K, Ohnuki T, Hattori K, Watanabe K, Nagatomo T: Tamsulosin: assessment of affinityof (3)H-P razosin binding to two alpha-1- adrenoceptor subtypes in the canine aorta. Pharmacology. 1999 Nov;59(5):234-8. Pubmed
  3. Sassard J, Zech PY, Pozet N, Cuisinaud G, Vincent M: [Comparative effects of an alpha 1 and beta 1-2 blocker (labetalol) and a beta-1 blocker (atenolol) in the hypertensive patient] J Pharmacol. 1983;14 Suppl 2:121-9. Pubmed
  4. Pedersen ME, Cockcroft JR: The vasodilatory beta-blockers. Curr Hypertens Rep. 2007 Aug;9(4):269-77. Pubmed
  5. Shiraishi K, Moriya M, Miyake N, Takayanagi I: Alpha 1-adrenoceptor blocking activities of bevantolol hydrochloride(NC-1400) and labetalol in rat isolated thoracic aorta—do they distinguish between subtypes? Gen Pharmacol. 1992 Sep;23(5):843-5. Pubmed
  6. Rosendorff C: Beta-blocking agents with vasodilator activity. J Hypertens Suppl. 1993 Jun;11(4):S37-40. Pubmed
  7. van Zwieten PA: An overview of the pharmacodynamic properties and therapeutic potential of combined alpha- and beta-adrenoceptor antagonists. Drugs. 1993 Apr;45(4):509-17. Pubmed

Enzymes

1. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on May 05, 2014 12:21