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

Description
Curator's Comment:: description was created based on several sources, including 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

5.8656961E11
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 (max)
Highest studied dose
Dose: 3000 mg
Route: oral
Route: single
Dose: 3000 mg
Sources:
unhealthy, 18-81
n = 32
Health Status: unhealthy
Condition: Hypertension
Age Group: 18-81
Sex: M+F
Population Size: 32
Sources:
Disc. AE: Orthostatic hypotension...
AEs leading to
discontinuation/dose reduction:
Orthostatic hypotension
Sources:
14 g single, oral (max)
Overdose
Dose: 14 g
Route: oral
Route: single
Dose: 14 g
Co-administed with::
alcohol, p.o
Sources:
healthy, 38
n = 1
Health Status: healthy
Age Group: 38
Sex: F
Population Size: 1
Sources:
Disc. AE: Acute renal failure...
AEs leading to
discontinuation/dose reduction:
Acute renal failure
Sources:
1200 mg 2 times / day multiple, oral (total daily dose)
Recommended
unhealthy
400 mg 2 times / day multiple, oral (max)
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Hypertension
Sources: Page: p.5
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
Sources: Page: p.5
300 mg single, intravenous (total)
Studied dose
Dose: 300 mg
Route: intravenous
Route: single
Dose: 300 mg
Sources: Page: p.14
unhealthy
Health Status: unhealthy
Condition: Hypertension
Sources: Page: p.14
AEs

AEs

AESignificanceDosePopulation
Orthostatic hypotension Disc. AE
3000 mg single, oral (max)
Highest studied dose
Dose: 3000 mg
Route: oral
Route: single
Dose: 3000 mg
Sources:
unhealthy, 18-81
n = 32
Health Status: unhealthy
Condition: Hypertension
Age Group: 18-81
Sex: M+F
Population Size: 32
Sources:
Acute renal failure Disc. AE
14 g single, oral (max)
Overdose
Dose: 14 g
Route: oral
Route: single
Dose: 14 g
Co-administed with::
alcohol, p.o
Sources:
healthy, 38
n = 1
Health Status: healthy
Age Group: 38
Sex: F
Population Size: 1
Sources:
Congestive heart failure
400 mg 2 times / day multiple, oral (max)
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Hypertension
Sources: Page: p.5
Cardiac failure Disc. AE
400 mg 2 times / day multiple, oral (max)
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Hypertension
Sources: Page: p.5
Hepatocellular injury severe, rare
400 mg 2 times / day multiple, oral (max)
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Hypertension
Sources: Page: p.5
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
[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
Acute myocardial infarction as a complication of clonidine withdrawal.
2003 Nov
[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
In Vitro Use Guide
Curator's Comment:: The effects of the alpha-beta-adrenergic antagonist labetalol on the activation of human platelets by adrenaline and other aggregating stimuli have been investigated. Labetalol inhibited platelet aggregation and secretion induced by collagen and the second phase of aggregation caused by ADP, platelet activating factor, adrenaline and ionophore A23187.
Unknown
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