LABETALOL HYDROCHLORIDE

Details

Stereochemistry	MIXED
Molecular Formula	C19H24N2O3.ClH
Molecular Weight	364.866
Optical Activity	UNSPECIFIED
Defined Stereocenters	0 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CC(CCC1=CC=CC=C1)NCC(O)C2=CC=C(O)C(=C2)C(N)=O

InChI

InChIKey=WQVZLXWQESQGIF-UHFFFAOYSA-N

InChI=1S/C19H24N2O3.ClH/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);1H

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 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 567 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/98/74787_Labetalol%20Hydrochloride_Prntlbl.pdf	Primary		Approved 8429	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 1988

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 57	UGT1A6 307 UGT2B4 249 P-gp 1537 UGT enzymes 27 UGT1A1 418 UGT1A9 380 UGT1A4 347 CYP 270

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
Ca2+ channels 60	inhibitor 3277 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 270	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/98/74989_Labetalol%20Hydrochloride.pdf	likely
UGT enzymes 27	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/98/75133_Labetalol%20Hydrochloride.pdf Page: 5.0	likely
UGT1A9 380	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18098064/	minor
UGT1A4 347	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18098064/	no
UGT1A6 307	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18098064/	no
UGT2B4 249	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18098064/	no
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24735251/	yes
UGT1A1 418	substrate 3367 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 effects of labetalol in man.	1976 Aug	10949
Letter: Emergency treatment of hypertensive crisis following clonidine withdrawal.	1976 May 29	1268685
A randomized, double-blind trial of oral nifedipine and intravenous labetalol in hypertensive emergencies of pregnancy.	1999 Oct	10521742
Affinities at the verapamil binding site of MDR1-encoded P-glycoprotein: drugs and analogs, stereoisomers and metabolites.	2000 Apr	10783826
Effects of labetalol treatment on the physiological and subjective response to smoked cocaine.	2000 Feb	10672977
A comparative study between a calcium channel blocker (Nicardipine) and a combined alpha-beta-blocker (Labetalol) for the control of emergence hypertension during craniotomy for tumor surgery.	2000 Oct	11004045
Studies on the photostability and in vitro phototoxicity of Labetalol.	2001 Feb	11231117
Hypoperfusion without ischemia surrounding acute intracerebral hemorrhage.	2001 Jul	11435792
Autoregulation of cerebral blood flow surrounding acute (6 to 22 hours) intracerebral hemorrhage.	2001 Jul 10	11445622
Norepinephrine release after acute brain death abolishes the cardioprotective effects of ischemic preconditioning in rabbit.	2001 Mar	11251272
[Hypertension emergency during surgery of renal carcinoma associated with non-diagnosed pheochromocytoma].	2001 Sep	11692436
Evidence of functional myocardial ischemia associated with myocardial dysfunction in brain-dead pigs.	2001 Sep 18	11568055
Liddle syndrome in a newborn infant.	2002 Aug	12185466
Remifentanil provides hemodynamic stability and faster awakening time in transsphenoidal surgery.	2002 Jan	11772821
Labetalol for prophylactic treatment of intractable migraine during pregnancy.	2002 Jul-Aug	12482217
Pemoline ingestion in children: a report of five cases and review of the literature.	2002 Mar	11865963
Acute and chronic hypertensive headache and hypertensive encephalopathy.	2002 May	12100095
Comprehensive management of hypertensive emergencies and urgencies.	2002 Nov-Dec	12441013
Short-term treatment of severe hypertension of pregnancy: prospective comparison of nicardipine and labetalol.	2002 Sep	12209278
Improvement of peak shape and separation performance of beta-blockers in conventional reversed-phase columns using solvent modifiers.	2003 Aug	12908951
Was case report a case of unrecognized local anesthetic toxicity?	2003 Jun	12761032
Clinical review: the management of hypertensive crises.	2003 Oct	12974970
Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis.	2003 Oct 25	14576246
A survey of Canadian practitioners regarding the management of the hypertensive disorders of pregnancy.	2004	15117601
In vitro effects of antihypertensive drugs on thromboxane agonist (U46619)-induced vasoconstriction in human internal mammary artery.	2004 Aug	15169740
Polymeric alkenoxy amino acid surfactants: II. Chiral separations of beta-blockers with multiple stereogenic centers.	2004 Mar	15004846
[Surgery to save body-packers].	2004 May	15158240

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 HYDROCHLORIDE

Official Name

English

LABETALOL HYDROCHLORIDE [JAN]

Common Name

English

TRANDATE

Brand Name

English

IBIDOMIDE HYDROCHLORIDE

Common Name

English

NORMODYNE

Brand Name

English

LABETALOL HYDROCHLORIDE [MART.]

Common Name

English

5-[1-Hydroxy-2-[(1-methyl-3-phenylpropyl)amino]ethyl]salicylamide monohydrochloride

Systematic Name

English

LABETALOL HYDROCHLORIDE [EP MONOGRAPH]

Common Name

English

LABETALOL HYDROCHLORIDE [USP MONOGRAPH]

Common Name

English

Labetalol hydrochloride [WHO-DD]

Common Name

English

LABETALOL HYDROCHLORIDE COMPONENT OF NORMOZIDE

Common Name

English

LABETALOL HCL

Common Name

English

AH 5158A

Code

English

SCH 15719W

Code

English

AH-5158A

Code

English

LABETALOL HYDROCHLORIDE [MI]

Common Name

English

LABETALOL HYDROCHLORIDE [VANDF]

Common Name

English

SCH-15719W

Code

English

BENZAMIDE, 2-HYDROXY-5-(1-HYDROXY-2-((1-METHYL-3-PHENYLPROPYL)AMINO)ETHYL)-, MONOHYDROCHLORIDE

Systematic Name

English

AH-5158A HYDROCHLORIDE

Code

English

LABETALOL HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

NSC-290312

Code

English

SCH-15719W HYDROCHLORIDE

Code

English

LABETALOL HYDROCHLORIDE [USAN]

Common Name

English

LABETALOL HYDROCHLORIDE [USP-RS]

Common Name

English

NORMOZIDE COMPONENT LABETALOL HYDROCHLORIDE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29713