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Identification
Name Labetalol
Accession Number DB00598 (APRD01062)
Type small molecule
Groups approved
Description

Blocker of both alpha- and beta-adrenergic receptors that is used as an antihypertensive. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Labetalol HCL
  • Labetalol hydrochloride
  • Labetalolum [INN-Latin]
  • Labetolol
Brand names
  • Albetol
  • Ibidomide
  • Normodyne
  • Presdate
  • Trandate
Brand name mixtures Not Available
Categories
  • Antihypertensive Agents
  • Adrenergic beta-Antagonists
  • Sympatholytics
  • Adrenergic alpha-Antagonists
CAS number 36894-69-6
Weight Average: 328.4055
Monoisotopic: 328.178692644
Chemical Formula C19H24N2O3
InChI Key InChIKey=SGUAFYQXFOLMHL-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)
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenethylamines
  • Phenylpropylamines
  • Benzamides
Substructures
  • Hydroxy Compounds
  • Benzyl Alcohols and Derivatives
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Amino Ketones
  • Benzene and Derivatives
  • Carbamates and Derivatives
  • Amino Alcohols
  • Phenethylamines
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Phenylpropylamines
  • Benzoyl Derivatives
  • Carboxylic Acids and Derivatives
  • Alcohols and Polyols
  • Phenyl Esters
  • Benzamides
Pharmacology
Indication For 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.
Pharmacodynamics Labetalol 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 action Labetalol 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.
Absorption Completely 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 distribution Not Available
Protein binding 50%
Metabolism

Primarily hepatic, undergoes significant first pass metabolism
Route of elimination These metabolites are present in plasma and are excreted in the urine, and via the bile, into the feces.
Half life 6-8 hours
Clearance Not Available
Toxicity LD50 = 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
Pathway Name SMPDB ID
Smp00368 Labetalol Pathway SMP00368
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
Form Route Strength
Liquid Intravenous
Tablet Oral
Prices
Unit description Cost Unit
Labetalol Hydrochloride 5 mg/ml 1.36 USD ml
Trandate 300 mg tablet 1.28 USD tablet
Trandate 5 mg/ml vial 1.25 USD ml
Trandate 200 mg tablet 1.08 USD tablet
Labetalol hcl 300 mg tablet 1.02 USD tablet
Normodyne 200 mg tablet 1.0 USD tablet
Labetalol hcl 200 mg tablet 0.76 USD tablet
Trandate 100 mg tablet 0.68 USD tablet
Labetalol hcl 100 mg tablet 0.53 USD tablet
Trandate 200 mg Tablet 0.47 USD tablet
Trandate 100 mg Tablet 0.27 USD tablet
Labetalol hcl 5 mg/ml vial 0.1 USD ml
Patents Not Available
Properties
State solid
Melting point 195-196 oC
Experimental Properties
Property Value Source
water solubility 20 mg/ml (HCl salt) PhysProp
logP 2.7 PhysProp
Caco2 permeability -5.03 [ADME Research, USCD] BiGG
Predicted Properties
Property Value Source
water solubility 5.78e-03 g/l ALOGPS
logP 1.73 ALOGPS
logP 1.34 ChemAxon Molconvert
logS -4.75 ALOGPS
pKa 14.11 ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 4 ChemAxon Molconvert
polar surface area 95.58 ChemAxon Molconvert
rotatable bond count 8 ChemAxon Molconvert
refractivity 94.72 ChemAxon Molconvert
polarizability 36.83 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C07063 Link_out
PubChem Compound 3869 Link_out
PubChem Substance 46505511 Link_out
ChemSpider 3734 Link_out
BindingDB 25758 Link_out
ChEBI 6343 Link_out
ChEMBL 6343 Link_out
Therapeutic Targets Database DAP000038 Link_out
PharmGKB PA450155 Link_out
Drug Product Database 2243539 Link_out
RxList http://www.rxlist.com/cgi/generic2/labet.htm Link_out
Drugs.com http://www.drugs.com/cdi/labetalol.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/nor1301.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Labetalol Link_out
ATC Codes
  • C07AG01
AHFS Codes
  • 24:24.00
PDB Entries Not Available
FDA label show (400.7 KB)
MSDS show (53.7 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Take without regard to meals.
Targets

1. Beta-1 adrenergic receptor

Pharmacological action: yes
Actions: antagonist

Beta-adrenergic receptors mediate the catecholamine- induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity

Organism class: human
UniProt ID: P08588 Link_out
Gene: ADRB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: antagonist

Beta-adrenergic receptors mediate the catecholamine- induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine

Organism class: human
UniProt ID: P07550 Link_out
Gene: ADRB2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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-1A adrenergic receptor

Pharmacological action: yes
Actions: antagonist

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins

Organism class: human
UniProt ID: P35348 Link_out
Gene: ADRA1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. 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

4. Alpha-1B adrenergic receptor

Pharmacological action: yes
Actions: antagonist

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system

Organism class: human
UniProt ID: P35368 Link_out
Gene: ADRA1B Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate, inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:05

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.