LABETALOL

Details

Stereochemistry	MIXED
Molecular Formula	C19H24N2O3
Molecular Weight	328.4055
Optical Activity	UNSPECIFIED
Defined Stereocenters	0 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(CCC1=CC=CC=C1)NCC(O)C2=CC=C(O)C(=C2)C(N)=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
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/98/74787_Labetalol%20Hydrochloride_Prntlbl.pdf
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

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Adrenergic receptor 35 Target ID: CHEMBL2331074 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6355664	Antagonist 2760

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 549 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/98/74787_Labetalol%20Hydrochloride_Prntlbl.pdf	Primary		Approved 8360	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

C_max

Value	Dose	Co-administered	Analyte	Population
72.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16225568/	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

Value	Dose	Co-administered	Analyte	Population
571 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16225568/	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

Dose	Population	Adverse events
3000 mg single, oral (max) Highest studied dose Dose: 3000 mg Route: oral Route: single Dose: 3000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/7433343	unhealthy, 18-81 n = 32 Health Status: unhealthy Condition: Hypertension Age Group: 18-81 Sex: M+F Population Size: 32 Sources: https://pubmed.ncbi.nlm.nih.gov/7433343	Disc. AE: Orthostatic hypotension... AEs leading to discontinuation/dose reduction: Orthostatic hypotension Sources: https://pubmed.ncbi.nlm.nih.gov/7433343
14 g single, oral (max) Overdose Dose: 14 g Route: oral Route: single Dose: 14 g Co-administed with:: alcohol, p.o Sources: https://pubmed.ncbi.nlm.nih.gov/29147632	healthy, 38 n = 1 Health Status: healthy Age Group: 38 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/29147632	Disc. AE: Acute renal failure... AEs leading to discontinuation/dose reduction: Acute renal failure Sources: https://pubmed.ncbi.nlm.nih.gov/29147632
1200 mg 2 times / day multiple, oral (total daily dose) Recommended Dose: 1200 mg, 2 times / day Route: oral Route: multiple Dose: 1200 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018716s026lbl.pdf https://www.ebmconsult.com/articles/monograph-labetalol-normodyne-trandate https://www.pdr.net/drug-summary/Labetalol-Hydrochloride-Injection-labetalol-hydrochloride-1568	unhealthy Health Status: unhealthy Condition: Hypertension Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018716s026lbl.pdf https://www.ebmconsult.com/articles/monograph-labetalol-normodyne-trandate https://www.pdr.net/drug-summary/Labetalol-Hydrochloride-Injection-labetalol-hydrochloride-1568	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018716s026lbl.pdf https://www.ebmconsult.com/articles/monograph-labetalol-normodyne-trandate https://www.pdr.net/drug-summary/Labetalol-Hydrochloride-Injection-labetalol-hydrochloride-1568
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018716s026lbl.pdf Page: p.5	unhealthy Health Status: unhealthy Condition: Hypertension Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018716s026lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018716s026lbl.pdf Page: p.5
300 mg single, intravenous (total) Studied dose Dose: 300 mg Route: intravenous Route: single Dose: 300 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019425s021lbl.pdf Page: p.14	unhealthy Health Status: unhealthy Condition: Hypertension Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019425s021lbl.pdf Page: p.14	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019425s021lbl.pdf Page: p.14

AEs

AE	Significance	Dose	Population
Orthostatic hypotension	Disc. AE	3000 mg single, oral (max) Highest studied dose Dose: 3000 mg Route: oral Route: single Dose: 3000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/7433343	unhealthy, 18-81 n = 32 Health Status: unhealthy Condition: Hypertension Age Group: 18-81 Sex: M+F Population Size: 32 Sources: https://pubmed.ncbi.nlm.nih.gov/7433343
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: https://pubmed.ncbi.nlm.nih.gov/29147632	healthy, 38 n = 1 Health Status: healthy Age Group: 38 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/29147632
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018716s026lbl.pdf Page: p.5	unhealthy Health Status: unhealthy Condition: Hypertension Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018716s026lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018716s026lbl.pdf Page: p.5	unhealthy Health Status: unhealthy Condition: Hypertension Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018716s026lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018716s026lbl.pdf Page: p.5	unhealthy Health Status: unhealthy Condition: Hypertension Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018716s026lbl.pdf Page: p.5

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
Ca2+ channels 41	UGT1A6 307 UGT2B4 249 P-gp 1527 UGT enzymes 27 UGT1A1 418 UGT1A9 380 UGT1A4 347 CYP 266

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
Ca2+ channels 44	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/98/75133_Labetalol%20Hydrochloride.pdf Page: 5.0	likely

Drug as victim

Target	Modality	Activity
CYP 266	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/98/74989_Labetalol%20Hydrochloride.pdf	likely
UGT enzymes 27	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/98/75133_Labetalol%20Hydrochloride.pdf Page: 5.0	likely
UGT1A9 380	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/18098064/	minor
UGT1A4 347	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/18098064/	no
UGT1A6 307	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/18098064/	no
UGT2B4 249	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/18098064/	no
P-gp 1527	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/24735251/	yes
UGT1A1 418	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/18098064/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:6343	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6343
ChemicalBook	CB7735086	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7735086
MolPort	MolPort-003-898-140	https://www.molport.com/shop/molecule-link/MolPort-003-898-140
eMolecules	653717	https://www.emolecules.com/cgi-bin/more?vid=653717

PubMed

Title	Date	PubMed
Labetalol (AH5158), a competitive alpha- and beta-receptor blocking drug, in the management of hypertension.	1976 Aug	14627
Pharmacological basis for antihypertensive effects of intravenous labetalol.	1977 Jan	12778
Hemiparesis after single minibolus of labetalol for hypertensive encephalopathy.	1979 Sep 15	115540
Hemodynamic collapse following labetalol administration in preeclampsia.	1992 Feb	1316047
Hypersensitivity immune reaction as a mechanism for dilevalol-associated hepatitis.	1992 Jul-Aug	1504402
Pharmacological effects of an aldehyde type alpha/beta-adrenoceptor blocking agent with vasodilating properties.	2000 Jun	11483288
Factor analysis, including antihypertensive medication, of the outcome of pregnancy in pregnancy-associated hypertension.	2001	11435745
Drugs in pregnancy. Antihypertensives.	2001 Dec	11800527
Role of alpha1-blockade in congenital long QT syndrome: investigation by exercise stress test.	2001 Jul	11446501
Hypoperfusion without ischemia surrounding acute intracerebral hemorrhage.	2001 Jul	11435792
Monitored anesthesia care using remifentanil and propofol for awake craniotomy.	2001 Jul	11426102
A new aspect of view in synthesizing new type beta-adrenoceptor blockers with ancillary antioxidant activities.	2001 Jul	11425575
Autoregulation of cerebral blood flow surrounding acute (6 to 22 hours) intracerebral hemorrhage.	2001 Jul 10	11445622
Non-aqueous capillary electrophoretic separation of enantiomeric amines with (-)-2,3:4,6-di-O-isopropylidene-2-keto-L-gulonic acid as chiral counter ion.	2001 Jul 13	11486876
Liddle syndrome in a newborn infant.	2002 Aug	12185466
Postpartum eclampsia.	2002 Aug 1	12182515
Elevated vascular resistance after labetalol during resection of a pheochromocytoma (brief report).	2002 Feb	11823392
Pheochromocytoma.	2002 Jan-Feb	11790269
[Nuclear medicine diagnosis of pheochromocytoma with metaiodobenzylguanidine].	2002 Jul	12584993
Labetalol for prophylactic treatment of intractable migraine during pregnancy.	2002 Jul-Aug	12482217
Labetalol-induced hyperkalemia in renal transplant recipients.	2002 Jul-Aug	12169866
Effects of hemoconcentration and sympathetic activation on serum lipid responses to brief mental stress.	2002 Jul-Aug	12140348
Acute and chronic hypertensive headache and hypertensive encephalopathy.	2002 May	12100095
The effect of antihypertensive drugs on the fetus.	2002 May	12082488
[Influence of labetalol on the resistance of human fetoplacental vessels in perfusion in vitro].	2002 Sep	12602277
Short-term treatment of severe hypertension of pregnancy: prospective comparison of nicardipine and labetalol.	2002 Sep	12209278
Scleroderma renal crisis sine scleroderma during pregnancy.	2003	12635948
Refractory hypotension during caesarean section following pre-operative administration of anti-hypertensive agents.	2003 Apr	15321504
Left ventricular diastolic function in pregnancy-induced hypertension.	2003 Apr	12784777
Labetalol treatment enhances the attenuation of tobacco withdrawal symptoms by nicotine in abstinent smokers.	2003 Dec	14668079
Managing hypertension in patients with stroke. Are you prepared for labetalol infusion?	2003 Jun	12830778
Acute myocardial infarction as a complication of clonidine withdrawal.	2003 Nov	14654180
[Posterior reversible encephalopathy syndrome].	2003 Nov-Dec	15114789
Enantioselective determination of arotinolol in human plasma by HPLC using teicoplanin chiral stationary phase.	2003 Oct	14598329
Fatality from administration of labetalol and crushed extended-release nifedipine.	2003 Oct	14519033
Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis.	2003 Oct 25	14576246
[Toxicologic analysis of some adrenergic-beta blockers in the diagnosis of intoxications].	2003 Oct-Dec	14971294
A survey of Canadian practitioners regarding the management of the hypertensive disorders of pregnancy.	2004	15117601
Very low-dose spinal anesthesia for cesarean section in a morbidly obese preeclamptic patient and its potential implications.	2004 Apr	15321413
Dexmedetomidine for awake carotid endarterectomy: efficacy, hemodynamic profile, and side effects.	2004 Apr	15021281
Simultaneous determination of thirteen beta-blockers and one metabolite by gradient high-performance liquid chromatography with photodiode-array UV detection.	2004 Apr 20	15066710
Hyponatremic hypertensive syndrome (HHS) in an 18-month old-child presenting as malignant hypertension: a case report.	2004 Apr 27	15113447
In vitro effects of antihypertensive drugs on thromboxane agonist (U46619)-induced vasoconstriction in human internal mammary artery.	2004 Aug	15169740
Chiral separation of labetalol stereoisomers in human plasma by capillary electrophoresis.	2004 Feb 20	14971505
Periprocedural hypertension: current concepts in management for the vascular surgeon.	2004 Jul-Aug	15306955
[Protective effect of alpha beta-blockers on hypertensive target-organ damage].	2004 Mar	15171441
Polymeric alkenoxy amino acid surfactants: II. Chiral separations of beta-blockers with multiple stereogenic centers.	2004 Mar	15004846
Effect of beta-adrenergic antagonists on bioluminescence control in three species of brittlestars (Echinodermata: Ophiuroidea).	2004 May	15313447
[Surgery to save body-packers].	2004 May	15158240
Severe hypertension and massive proteinuria in a newborn with renal artery stenosis.	2004 May	14986083

Patents

Sample Use Guides

In Vivo Use Guide

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

Unknown

Name

Type

Language

LABETALOL

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

NBK547846