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Record Information
Version2.0
Creation Date2009-07-30 17:58:59 UTC
Update Date2014-12-24 20:26:07 UTC
Accession NumberT3D3517
Identification
Common NameLabetalol
ClassSmall Molecule
DescriptionLabetalol is only found in individuals that have used or taken this drug. It is a blocker of both alpha- and beta-adrenergic receptors that is used as an antihypertensive (PubChem). 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.
Compound Type
  • Adrenergic alpha-1 Receptor Antagonist
  • Adrenergic alpha-Antagonist
  • Adrenergic beta-Antagonist
  • Amide
  • Amine
  • Antihypertensive Agent
  • Drug
  • Ester
  • Metabolite
  • Organic Compound
  • Sympatholytic
  • Sympathomimetic
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
3-Carboxamido-4-hydroxy-alpha-((1-methyl-3-phenylpropylamino)methyl)benzyl alcohol
5-(1-Hydroxy-2-(1-methyl-3-phenylpropylamino)ethyl)salicylamide
Albetol
Labetalolum
Labetolol
Latol
Normadate
Normodyne
Trandate
Chemical FormulaC19H24N2O3
Average Molecular Mass328.406 g/mol
Monoisotopic Mass328.179 g/mol
CAS Registry Number36894-69-6
IUPAC Name2-hydroxy-5-{1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl}benzamide
Traditional Namelabetalol
SMILESCC(CCC1=CC=CC=C1)NCC(O)C1=CC(C(O)=N)=C(O)C=C1
InChI IdentifierInChI=1/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)
InChI KeyInChIKey=SGUAFYQXFOLMHL-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as salicylamides. These are carboxamide derivatives of salicylic acid. Salicylic acid is the ortho-hydroxylated derivative of benzoic acid.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzoic acids and derivatives
Direct ParentSalicylamides
Alternative Parents
Substituents
  • Salicylamide
  • Benzamide
  • Benzoyl
  • 1-hydroxy-2-unsubstituted benzenoid
  • Phenol
  • Aralkylamine
  • Vinylogous acid
  • Amino acid or derivatives
  • 1,2-aminoalcohol
  • Secondary alcohol
  • Carboxamide group
  • Primary carboxylic acid amide
  • Secondary amine
  • Carboxylic acid derivative
  • Secondary aliphatic amine
  • Organopnictogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Alcohol
  • Organic oxygen compound
  • Aromatic alcohol
  • Organic nitrogen compound
  • Amine
  • Hydrocarbon derivative
  • Organic oxide
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
Labetalol PathwayNot AvailableNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point188°C
Boiling PointNot Available
Solubility117 mg/L (at 25°C)
LogP3.09
Predicted Properties
PropertyValueSource
Water Solubility0.0058 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 Area95.58 ŲChemAxon
Rotatable Bond Count8ChemAxon
Refractivity94.72 m³·mol⁻¹ChemAxon
Polarizability36.83 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0900-4912000000-56ddcdc04cc33ad89c09JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-000i-1291200000-6bd93665242775341b9dJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-004i-0319000000-cd3fa186952809ae3558JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-03di-0519000000-0a8da4acfa8cd259fb3fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-03dl-4928000000-117458013dbd49aaf54bJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03fr-0119000000-6781a14791c4905bb7e7JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03dl-1976000000-b876781f8c7652506d0fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000x-7900000000-c0f1be1138aa87f4801dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0219000000-41a2556d51bec476196cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-056s-1937000000-4890a50d091b188ff95fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-5900000000-3a6780e7e0e66cea3105JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-03dl-7900000000-e18d52bcb93357c4a7e2JSpectraViewer | MoNA
Toxicity Profile
Route of ExposureOral, parenteral (intravenous injection). 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.
Mechanism of ToxicityLabetalol 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. 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. Beta-2-agonist activity has been demonstrated in animals with minimal beta-1-agonist (ISA) activity detected. In animals, at doses greater than those required for alpha- or beta- adrenergic blockade, a membrane stabilizing effect has been demonstrated.
MetabolismPrimarily 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
Toxicity ValuesLD50 = 66 mg/kg (Rat, parental-intravenous)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor 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.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSide effects or adverse reactions include dizziness when standing up, very low blood pressure, severely slow heartbeat, weakness, diminished sexual function, fatigue
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00598
HMDB IDHMDB14736
PubChem Compound ID3869
ChEMBL IDCHEMBL429
ChemSpider ID3734
KEGG IDC07063
UniProt IDNot Available
OMIM ID
ChEBI ID6343
BioCyc IDNot Available
CTD IDNot Available
Stitch IDLabetalol
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkLabetalol
References
Synthesis Reference

U.S. Patent 4,012,444.

MSDSLink
General ReferencesNot Available
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

1. Alpha-1 adrenergic receptors (Protein Group)
General Function:
Protein heterodimerization activity
Specific Function:
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. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Included Proteins:
P35348 , P35368 , P25100
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. [2696507 ]
  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. [10529655 ]
  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. [6355664 ]
  4. Pedersen ME, Cockcroft JR: The vasodilatory beta-blockers. Curr Hypertens Rep. 2007 Aug;9(4):269-77. [17686376 ]
  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. [1358746 ]
  6. Rosendorff C: Beta-blocking agents with vasodilator activity. J Hypertens Suppl. 1993 Jun;11(4):S37-40. [8104240 ]
  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. [7684671 ]
General Function:
Receptor signaling protein activity
Specific Function:
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. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling.
Gene Name:
ADRB1
Uniprot ID:
P08588
Molecular Weight:
51322.1 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Dissociation0.0235 uMNot AvailableBindingDB 25758
Dissociation0.03162 uMNot AvailableBindingDB 25758
References
  1. Baker JG: The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors. Br J Pharmacol. 2005 Feb;144(3):317-22. [15655528 ]
  2. Asselin AA, Humber LG, Crosilla D, Oshiro G, Wojdan A, Grimes D, Heaslip RJ, Rimele TJ, Shaw CC: Indole-phenol bioisosterism. Synthesis and antihypertensive activity of a pyrrolo analogue of labetalol. J Med Chem. 1986 Jun;29(6):1009-15. [3012084 ]
General Function:
Protein homodimerization activity
Specific Function:
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.
Gene Name:
ADRB2
Uniprot ID:
P07550
Molecular Weight:
46458.32 Da
References
  1. Wisler JW, DeWire SM, Whalen EJ, Violin JD, Drake MT, Ahn S, Shenoy SK, Lefkowitz RJ: A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling. Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16657-62. Epub 2007 Oct 9. [17925438 ]
General Function:
Protein homodimerization activity
Specific Function:
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. Beta-3 is involved in the regulation of lipolysis and thermogenesis.
Gene Name:
ADRB3
Uniprot ID:
P13945
Molecular Weight:
43518.615 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Dissociation0.661 uMNot AvailableBindingDB 25758
References
  1. Baker JG: The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors. Br J Pharmacol. 2005 Feb;144(3):317-22. [15655528 ]
General Function:
Syndecan binding
Specific Function:
Endoglycosidase that cleaves heparan sulfate proteoglycans (HSPGs) into heparan sulfate side chains and core proteoglycans. Participates in extracellular matrix (ECM) degradation and remodeling. Selectively cleaves the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying either a 3-O-sulfo or a 6-O-sulfo group. Can also cleave the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying a 2-O-sulfo group, but not linkages between a glucuronic acid unit and a 2-O-sulfated iduronic acid moiety. It is essentially inactive at neutral pH but becomes active under acidic conditions such as during tumor invasion and in inflammatory processes. Facilitates cell migration associated with metastasis, wound healing and inflammation. Enhances shedding of syndecans, and increases endothelial invasion and angiogenesis in myelomas. Acts as procoagulant by increasing the generation of activation factor X in the presence of tissue factor and activation factor VII. Increases cell adhesion to the extacellular matrix (ECM), independent of its enzymatic activity. Induces AKT1/PKB phosphorylation via lipid rafts increasing cell mobility and invasion. Heparin increases this AKT1/PKB activation. Regulates osteogenesis. Enhances angiogenesis through up-regulation of SRC-mediated activation of VEGF. Implicated in hair follicle inner root sheath differentiation and hair homeostasis.
Gene Name:
HPSE
Uniprot ID:
Q9Y251
Molecular Weight:
61148.17 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Dissociation1000 uMNot AvailableBindingDB 25758
References
  1. Gozalbes R, Mosulen S, Orti L, Rodriguez-Diaz J, Carbajo RJ, Melnyk P, Pineda-Lucena A: Hit identification of novel heparanase inhibitors by structure- and ligand-based approaches. Bioorg Med Chem. 2013 Apr 1;21(7):1944-51. doi: 10.1016/j.bmc.2013.01.033. Epub 2013 Jan 31. [23415087 ]
General Function:
Protein heterodimerization activity
Specific Function:
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. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1A
Uniprot ID:
P35348
Molecular Weight:
51486.005 Da
General Function:
Protein heterodimerization activity
Specific Function:
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. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1B
Uniprot ID:
P35368
Molecular Weight:
56835.375 Da