U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry MIXED
Molecular Formula C19H24N2O3
Molecular Weight 328.4062
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LABETALOL

SMILES

CC(CCc1ccccc1)NCC(c2ccc(c(c2)C(=N)O)O)O

InChI

InChIKey=SGUAFYQXFOLMHL-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C19H24N2O3
Molecular Weight 328.4062
Charge 0
Count
Stereochemistry MIXED
Additional Stereochemistry No
Defined Stereocenters 0 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: http://www.rxlist.com/trandate-drug.htm

Labetalol is a blocker of both alpha- and beta-adrenergic receptors that is used as an antihypertensive. It may be used alone or in combination with other antihypertensive agents, especially thiazide and loop diuretics. The capacity of labetalol HCl to block alpha receptors in man has been demonstrated by attenuation of the pressor effect of phenylephrine and by a significant reduction of the pressor response caused by immersing the hand in ice-cold water ("cold-pressor test"). Labetalol HCl's beta1-receptor blockade in man was demonstrated by a small decrease in the resting heart rate, attenuation of tachycardia produced by isoproterenol or exercise, and by attenuation of the reflex tachycardia to the hypotension produced by amyl nitrite. Beta2-receptor blockade was demonstrated by inhibition of the isoproterenol-induced fall in diastolic blood pressure. Both the alpha- and beta-blocking actions of orally administered labetalol HCl contribute to a decrease in blood pressure in hypertensive patients. Labetalol HCl consistently, in dose-related fashion, blunted increases in exercise-induced blood pressure and heart rate, and in their double product. The pulmonary circulation during exercise was not affected by labetalol HCl dosing. Single oral doses of labetalol HCl administered to patients with coronary artery disease had no significant effect on sinus rate, intraventricular conduction, or QRS duration. The atrioventricular (A-V) conduction time was modestly prolonged in two of seven patients. In another study, IV labetalol HCl slightly prolonged A-V nodal conduction time and atrial effective refractory period with only small changes in heart rate. The metabolism of labetalol is mainly through conjugation to glucuronide metabolites. These metabolites are present in plasma and are excreted in the urine and, via the bile, into the feces. Approximately 55% to 60% of a dose appears in the urine as conjugates or unchanged labetalol within the first 24 hours of dosing. Labetalol has been shown to cross the placental barrier in humans. Only negligible amounts of the drug crossed the blood-brain barrier in animal studies. Labetalol is approximately 50% protein bound. Neither hemodialysis nor peritoneal dialysis removes a significant amount of labetalol HCl from the general circulation.

CNS Activity

Curator's Comment:: Labetalol has been shown to cross the placental barrier in humans. Only negligible amounts of the drug crossed the blood-brain barrier in animal studies.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
LABETALOL HYDROCHLORIDE

Approved Use

Labetalol hydrochloride tablets, USP are indicated in the management of hypertension. Labetalol hydrochloride tablets, USP may be used alone or in combination with other antihypertensive agents, especially thiazide and loop diuretics.

Launch Date

586569600000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
72.4 ng/mL
100 mg 2 times / 2 days steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
LABETALOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
571 ng × h/mL
100 mg 2 times / 2 days steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
LABETALOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
3000 mg single, oral
Highest studied dose
dose: 3000 mg
route: oral
experiment_type: single
dose_type: Highest studied dose
co-adm with
    data_source:
    https://pubmed.ncbi.nlm.nih.gov/7433343
    unhealthy, 18-81
    population: unhealthy
    age: 18-81
    sex: M+F
    food_status:
    n:
    data_source:
    https://pubmed.ncbi.nlm.nih.gov/7433343
    Disc. AE: Orthostatic hypotension...
    AEs leading to
    discontinuation/dose reduction:​
    Orthostatic hypotension

    data_source:
    https://pubmed.ncbi.nlm.nih.gov/7433343
    14 g single, oral
    Overdose
    dose: 14 g
    route: oral
    experiment_type: single
    dose_type: Overdose
    co-adm with
      data_source:
      https://pubmed.ncbi.nlm.nih.gov/29147632
      healthy, 38
      population: healthy
      age: 38
      sex: F
      food_status:
      n:
      data_source:
      https://pubmed.ncbi.nlm.nih.gov/29147632
      Disc. AE: Acute renal failure...
      AEs leading to
      discontinuation/dose reduction:​
      Acute renal failure

      data_source:
      https://pubmed.ncbi.nlm.nih.gov/29147632
      1200 mg 2 times / day multiple, oral
      Recommended
      unhealthy
      400 mg 2 times / day multiple, oral
      Recommended
      dose: 400 mg 2 times / day
      route: oral
      experiment_type: multiple
      dose_type: Recommended
      co-adm with
        data_source:
        https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018716s026lbl.pdf
        unhealthy
        population: unhealthy
        age:
        sex:
        food_status:
        n:
        data_source:
        https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018716s026lbl.pdf
        Disc. AE: Cardiac failure...
        Other AEs: Hepatocellular injury, Congestive heart failure...
        AEs leading to
        discontinuation/dose reduction:​
        Cardiac failure

        Other AEs:
        Hepatocellular injury (severe, rare)
        Congestive heart failure

        data_source:
        https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018716s026lbl.pdf
        300 mg single, intravenous
        Studied dose
        dose: 300 mg
        route: intravenous
        experiment_type: single
        dose_type: Studied dose
        co-adm with
          data_source:
          https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019425s021lbl.pdf
          unhealthy
          population: unhealthy
          age:
          sex:
          food_status:
          n:
          data_source:
          https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019425s021lbl.pdf
          AEs

          AEs

          AESignificanceDosePopulation
          Acute renal failure
          Disc. AE
          14 g single, oral
          Overdose
          dose: 14 g
          route: oral
          experiment_type: single
          dose_type: Overdose
          co-adm with
            data_source:
            https://pubmed.ncbi.nlm.nih.gov/29147632
            healthy, 38
            population:
            age:
            sex:
            food_status:
            n:
            data_source:
            https://pubmed.ncbi.nlm.nih.gov/29147632
            Orthostatic hypotension
            Disc. AE
            3000 mg single, oral
            Highest studied dose
            dose: 3000 mg
            route: oral
            experiment_type: single
            dose_type: Highest studied dose
            co-adm with
              data_source:
              https://pubmed.ncbi.nlm.nih.gov/7433343
              unhealthy, 18-81
              population:
              age:
              sex:
              food_status:
              n:
              data_source:
              https://pubmed.ncbi.nlm.nih.gov/7433343
              Congestive heart failure
              400 mg 2 times / day multiple, oral
              Recommended
              dose: 400 mg 2 times / day
              route: oral
              experiment_type: multiple
              dose_type: Recommended
              co-adm with
                data_source:
                https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018716s026lbl.pdf
                unhealthy
                population:
                age:
                sex:
                food_status:
                n:
                data_source:
                https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018716s026lbl.pdf
                Cardiac failure
                Disc. AE
                400 mg 2 times / day multiple, oral
                Recommended
                dose: 400 mg 2 times / day
                route: oral
                experiment_type: multiple
                dose_type: Recommended
                co-adm with
                  data_source:
                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018716s026lbl.pdf
                  unhealthy
                  population:
                  age:
                  sex:
                  food_status:
                  n:
                  data_source:
                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018716s026lbl.pdf
                  Hepatocellular injury severe,rare%
                  400 mg 2 times / day multiple, oral
                  Recommended
                  dose: 400 mg 2 times / day
                  route: oral
                  experiment_type: multiple
                  dose_type: Recommended
                  co-adm with
                    data_source:
                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018716s026lbl.pdf
                    unhealthy
                    population:
                    age:
                    sex:
                    food_status:
                    n:
                    data_source:
                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018716s026lbl.pdf
                    PubMed

                    PubMed

                    TitleDatePubMed
                    Labetalol (AH5158), a competitive alpha- and beta-receptor blocking drug, in the management of hypertension.
                    1976 Aug
                    Letter: Emergency treatment of hypertensive crisis following clonidine withdrawal.
                    1976 May 29
                    Pharmacological basis for antihypertensive effects of intravenous labetalol.
                    1977 Jan
                    Hemodynamic collapse following labetalol administration in preeclampsia.
                    1992 Feb
                    Hypersensitivity immune reaction as a mechanism for dilevalol-associated hepatitis.
                    1992 Jul-Aug
                    Labetalol decreases cerebral perfusion pressure without negatively affecting cerebral blood flow in hypertensive gravidas.
                    2002
                    Factors influencing acute ischaemia-induced renal hypertension in rats.
                    2002 Dec
                    Cardiac arrest after labetalol and metoclopramide administration in a patient with scleroderma.
                    2002 Dec
                    Electrocardiographic changes associated with beta-blocker toxicity.
                    2002 Dec
                    Partial agonistic activity of labetalol, the arylethanolamine, on beta 3-adrenoceptors in the guinea-pig gastric fundus.
                    2002 Feb
                    [Nuclear medicine diagnosis of pheochromocytoma with metaiodobenzylguanidine].
                    2002 Jul
                    Labetalol for prophylactic treatment of intractable migraine during pregnancy.
                    2002 Jul-Aug
                    Spectrofluorometric determination of labetolol in pharmaceutical preparations and spiked human urine through the formation of coumarin derivative.
                    2002 Nov 7
                    Comprehensive management of hypertensive emergencies and urgencies.
                    2002 Nov-Dec
                    [Influence of labetalol on the resistance of human fetoplacental vessels in perfusion in vitro].
                    2002 Sep
                    Short-term treatment of severe hypertension of pregnancy: prospective comparison of nicardipine and labetalol.
                    2002 Sep
                    [Influence of different pharmacological agents in the ex vivo proliferation of mesothelial cells obtained from the peritoneal effluent of patients treated with peritoneal dialysis].
                    2003
                    Scleroderma renal crisis sine scleroderma during pregnancy.
                    2003
                    Refractory hypotension during caesarean section following pre-operative administration of anti-hypertensive agents.
                    2003 Apr
                    Left ventricular diastolic function in pregnancy-induced hypertension.
                    2003 Apr
                    Spectrophotometric determination of labetalol in pharmaceutical preparations and spiked human urine.
                    2003 Apr
                    Multiple Bier blocks with labetalol for complex regional pain syndrome refractory to other treatments.
                    2003 Apr
                    The effect of remifentanil on seizure duration and acute hemodynamic responses to electroconvulsive therapy.
                    2003 Apr
                    Clonidine facilitates controlled hypotension in adolescent children.
                    2003 Apr
                    Improvement of peak shape and separation performance of beta-blockers in conventional reversed-phase columns using solvent modifiers.
                    2003 Aug
                    Labetalol treatment enhances the attenuation of tobacco withdrawal symptoms by nicotine in abstinent smokers.
                    2003 Dec
                    Managing hypertension in patients with stroke. Are you prepared for labetalol infusion?
                    2003 Jun
                    Agonist actions of "beta-blockers" provide evidence for two agonist activation sites or conformations of the human beta1-adrenoceptor.
                    2003 Jun
                    Was case report a case of unrecognized local anesthetic toxicity?
                    2003 Jun
                    Community-based thrombolytic therapy of acute ischemic stroke in Helsinki.
                    2003 Jun
                    Remifentanil for intraoperative analgesia during the endoscopic surgical treatment of pituitary lesions.
                    2003 Mar
                    [Posterior reversible encephalopathy syndrome].
                    2003 Nov-Dec
                    Enantioselective determination of arotinolol in human plasma by HPLC using teicoplanin chiral stationary phase.
                    2003 Oct
                    Fatality from administration of labetalol and crushed extended-release nifedipine.
                    2003 Oct
                    Clinical review: the management of hypertensive crises.
                    2003 Oct
                    Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis.
                    2003 Oct 25
                    [Toxicologic analysis of some adrenergic-beta blockers in the diagnosis of intoxications].
                    2003 Oct-Dec
                    A survey of Canadian practitioners regarding the management of the hypertensive disorders of pregnancy.
                    2004
                    Very low-dose spinal anesthesia for cesarean section in a morbidly obese preeclamptic patient and its potential implications.
                    2004 Apr
                    Dexmedetomidine for awake carotid endarterectomy: efficacy, hemodynamic profile, and side effects.
                    2004 Apr
                    Simultaneous determination of thirteen beta-blockers and one metabolite by gradient high-performance liquid chromatography with photodiode-array UV detection.
                    2004 Apr 20
                    Hyponatremic hypertensive syndrome (HHS) in an 18-month old-child presenting as malignant hypertension: a case report.
                    2004 Apr 27
                    In vitro effects of antihypertensive drugs on thromboxane agonist (U46619)-induced vasoconstriction in human internal mammary artery.
                    2004 Aug
                    Chiral separation of labetalol stereoisomers in human plasma by capillary electrophoresis.
                    2004 Feb 20
                    Periprocedural hypertension: current concepts in management for the vascular surgeon.
                    2004 Jul-Aug
                    [Protective effect of alpha beta-blockers on hypertensive target-organ damage].
                    2004 Mar
                    Polymeric alkenoxy amino acid surfactants: II. Chiral separations of beta-blockers with multiple stereogenic centers.
                    2004 Mar
                    Effect of beta-adrenergic antagonists on bioluminescence control in three species of brittlestars (Echinodermata: Ophiuroidea).
                    2004 May
                    [Surgery to save body-packers].
                    2004 May
                    Severe hypertension and massive proteinuria in a newborn with renal artery stenosis.
                    2004 May
                    Patents

                    Patents

                    Sample Use Guides

                    The recommended initial dosage is 100 mg twice daily whether used alone or added to a diuretic regimen. After 2 or 3 days, using standing blood pressure as an indicator, dosage may be titrated in increments of 100 mg b.i.d. every 2 or 3 days. The usual maintenance dosage of labetalol HCl is between 200 and 400 mg twice daily.
                    Route of Administration: Oral
                    Substance Class Chemical
                    Created
                    by admin
                    on Sat Jun 26 03:27:45 UTC 2021
                    Edited
                    by admin
                    on Sat Jun 26 03:27:45 UTC 2021
                    Record UNII
                    R5H8897N95
                    Record Status Validated (UNII)
                    Record Version
                    • Download
                    Name Type Language
                    LABETALOL
                    HSDB   INN   MI   VANDF   WHO-DD  
                    INN  
                    Official Name English
                    BENZAMIDE, 2-HYDROXY-5-(1-HYDROXY-2-((1-METHYL-3-PHENYLPROPYL)AMINO)ETHYL)-
                    Systematic Name English
                    AH-5158A FREE BASE
                    Code English
                    SCH-15719W FREE BASE
                    Code English
                    LABETALOL [HSDB]
                    Common Name English
                    LABETALOL [WHO-DD]
                    Common Name English
                    LABETALOL [VANDF]
                    Common Name English
                    IBIDOMIDE
                    Common Name English
                    LABETALOL [INN]
                    Common Name English
                    LABETALOL [MI]
                    Common Name English
                    Classification Tree Code System Code
                    LIVERTOX 536
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    NDF-RT N0000175556
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    WHO-ATC C07BG01
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    WHO-VATC QC07CG01
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    WHO-VATC QC07BG01
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    WHO-ATC C07CG01
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    WHO-ATC C07AG01
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    WHO-VATC QC07AG01
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    NDF-RT N0000000161
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    NCI_THESAURUS C72900
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    Code System Code Type Description
                    ChEMBL
                    CHEMBL429
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    PRIMARY
                    ECHA (EC/EINECS)
                    253-258-3
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    PRIMARY
                    WIKIPEDIA
                    LABETALOL
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    PRIMARY
                    PUBCHEM
                    3869
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    PRIMARY
                    MERCK INDEX
                    M6647
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    PRIMARY Merck Index
                    LACTMED
                    Labetalol
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    PRIMARY
                    MESH
                    D007741
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    PRIMARY
                    IUPHAR
                    7207
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    PRIMARY
                    RXCUI
                    6185
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    PRIMARY RxNorm
                    INN
                    3941
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    PRIMARY
                    CAS
                    36894-69-6
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    PRIMARY
                    EVMPD
                    SUB08382MIG
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    PRIMARY
                    FDA UNII
                    R5H8897N95
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    PRIMARY
                    DRUG CENTRAL
                    1531
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    PRIMARY
                    EPA CompTox
                    36894-69-6
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    PRIMARY
                    HSDB
                    6537
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    PRIMARY
                    NCI_THESAURUS
                    C29146
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    PRIMARY
                    DRUG BANK
                    DB00598
                    Created by admin on Sat Jun 26 03:27:45 UTC 2021 , Edited by admin on Sat Jun 26 03:27:45 UTC 2021
                    PRIMARY
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