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
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
DescriptionSources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/98/74787_Labetalol%20Hydrochloride_Prntlbl.pdfCurator's Comment: description was created based on several sources, including
http://www.rxlist.com/trandate-drug.htm
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.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2331074 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6355664 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | LABETALOL HYDROCHLORIDE Approved UseLabetalol 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 Date1988 |
Cmax
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 |
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 Dose: 1200 mg, 2 times / day Route: oral Route: multiple Dose: 1200 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Condition: Hypertension Sources: |
|
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) Sources: Page: p.5Congestive heart failure |
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
AE | Significance | Dose | Population |
---|---|---|---|
Orthostatic hypotension | Disc. AE | 3000 mg single, oral (max) Highest studied dose |
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 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/98/75133_Labetalol%20Hydrochloride.pdf Page: 5.0 |
likely |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
likely | ||||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/98/75133_Labetalol%20Hydrochloride.pdf Page: 5.0 |
likely | |||
minor | ||||
no | ||||
no | ||||
no | ||||
yes | ||||
yes |
PubMed
Title | Date | PubMed |
---|---|---|
Labetalol (AH5158), a competitive alpha- and beta-receptor blocking drug, in the management of hypertension. | 1976 Aug |
|
Pharmacological effects of labetalol in man. | 1976 Aug |
|
Letter: Emergency treatment of hypertensive crisis following clonidine withdrawal. | 1976 May 29 |
|
A randomized, double-blind trial of oral nifedipine and intravenous labetalol in hypertensive emergencies of pregnancy. | 1999 Oct |
|
Affinities at the verapamil binding site of MDR1-encoded P-glycoprotein: drugs and analogs, stereoisomers and metabolites. | 2000 Apr |
|
Effects of labetalol treatment on the physiological and subjective response to smoked cocaine. | 2000 Feb |
|
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 |
|
Studies on the photostability and in vitro phototoxicity of Labetalol. | 2001 Feb |
|
Hypoperfusion without ischemia surrounding acute intracerebral hemorrhage. | 2001 Jul |
|
Autoregulation of cerebral blood flow surrounding acute (6 to 22 hours) intracerebral hemorrhage. | 2001 Jul 10 |
|
Norepinephrine release after acute brain death abolishes the cardioprotective effects of ischemic preconditioning in rabbit. | 2001 Mar |
|
[Hypertension emergency during surgery of renal carcinoma associated with non-diagnosed pheochromocytoma]. | 2001 Sep |
|
Evidence of functional myocardial ischemia associated with myocardial dysfunction in brain-dead pigs. | 2001 Sep 18 |
|
Liddle syndrome in a newborn infant. | 2002 Aug |
|
Remifentanil provides hemodynamic stability and faster awakening time in transsphenoidal surgery. | 2002 Jan |
|
Labetalol for prophylactic treatment of intractable migraine during pregnancy. | 2002 Jul-Aug |
|
Pemoline ingestion in children: a report of five cases and review of the literature. | 2002 Mar |
|
Acute and chronic hypertensive headache and hypertensive encephalopathy. | 2002 May |
|
Comprehensive management of hypertensive emergencies and urgencies. | 2002 Nov-Dec |
|
Short-term treatment of severe hypertension of pregnancy: prospective comparison of nicardipine and labetalol. | 2002 Sep |
|
Improvement of peak shape and separation performance of beta-blockers in conventional reversed-phase columns using solvent modifiers. | 2003 Aug |
|
Was case report a case of unrecognized local anesthetic toxicity? | 2003 Jun |
|
Clinical review: the management of hypertensive crises. | 2003 Oct |
|
Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis. | 2003 Oct 25 |
|
A survey of Canadian practitioners regarding the management of the hypertensive disorders of pregnancy. | 2004 |
|
In vitro effects of antihypertensive drugs on thromboxane agonist (U46619)-induced vasoconstriction in human internal mammary artery. | 2004 Aug |
|
Polymeric alkenoxy amino acid surfactants: II. Chiral separations of beta-blockers with multiple stereogenic centers. | 2004 Mar |
|
[Surgery to save body-packers]. | 2004 May |
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2856060
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
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NCI_THESAURUS |
C29713
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ACTIVE MOIETY
SUBSTANCE RECORD