Labetalol HCl (ch15719W; AH5158; Normodyne, Albetol, Trandate, Apo-Labetalol, Dilevalol), the hydrochloride salt of Labetalol, is a competitive and dual antagonist of alpha1-adrenergic and beta-adrenergic receptors with potential antihypertensive properties. The medication labetalol was approved to treat hypertension.

Physicochemical Properties

Molecular Formula	C19H25CLN2O3
Molecular Weight	364.866404294968
Exact Mass	364.16
Elemental Analysis	C, 62.55; H, 6.91; Cl, 9.72; N, 7.68; O, 13.15
CAS #	32780-64-6
Related CAS #	Labetalol; 36894-69-6; Labetalol hydrochloride (Standard); 32780-64-6
PubChem CID	71412
Appearance	White to off-white crystalline powder
Density	1.2±0.1 g/cm3
Boiling Point	552.7±50.0 °C at 760 mmHg
Melting Point	187-189°
Flash Point	288.1±30.1 °C
Vapour Pressure	0.0±1.6 mmHg at 25°C
Index of Refraction	1.609
LogP	2.31
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	8
Heavy Atom Count	25
Complexity	385
Defined Atom Stereocenter Count	0
SMILES	O=C(N)C1=CC(C(O)CNC(C)CCC2=CC=CC=C2)=CC=C1O.[H]Cl
InChi Key	WQVZLXWQESQGIF-UHFFFAOYSA-N
InChi Code	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
Chemical Name	2-hydroxy-5-[1-hydroxy-2-(4-phenylbutan-2-ylamino)ethyl]benzamide;hydrochloride
Synonyms	AH-5158 hydrochloride; Sch-15719W; AH5158 hydrochloride; Sch15719W; AH 5158 hydrochloride; Sch 15719W; Normodyne; Trandate; Albetol; Apo-Labetalol; Dilevalol
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	α1-adrenergic receptor; β-adrenergic receptor
Toxicity/Toxicokinetics	Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Because of the low levels of labetalol in breastmilk, amounts ingested by the infant are small and would not be expected to cause any adverse effects in fullterm breastfed infants. No special precautions are required in most infants. However, other agents may be preferred while nursing a preterm infant. Labetalol may predispose nursing mothers to Raynaud’s phenomenon of the nipple. ◉ Effects in Breastfed Infants One investigator reported that no adverse effects occurred in breastfed infants whose mothers were taking labetalol in doses of 330 to 800 mg daily. A 26-week premature infant weighing 640 grams developed sinus bradycardia (80 to 90 bpm) and isolated atrial premature beats after nasogastric feeding with mother's pumped breastmilk began on day 8 of life. The mother was taking labetalol 300 mg twice daily by mouth for hypertension. Bradycardia and premature beats resolved within 24 hours of substitution of formula for breastmilk. No other causes for bradycardia could be identified. One untimed sample of the mother's breastmilk contained 710 mcg/L of labetalol. Although the authors estimated the infant's dose to be 100 mg/kg daily, a recalculation using their data indicates that the infant's dose was only 100 mcg/kg daily. A 2-month-old infant was being breastfed exclusively by a mother taking labetalol 100 mg twice daily. The infants electrocardiogram had a regular heart rate, but borderline prolonged QT. The infant was started on propranolol 1 mg/kg daily for infantile hemangioma. One month later, the infant had a normal QT interval. A second infant was exclusively breastfed by a mother taking labetalol 150 mg twice daily and nifedipine 60 mg daily. The infant was started on propranolol 0.6 mg/kg daily for infantile hemangioma. The propranolol dose was increased over 2 weeks to 3.4 mg/kg daily. The infant had some sleeping difficulties with the higher propranolol dose, but no other symptoms. ◉ Effects on Lactation and Breastmilk Intravenous labetalol can increase serum prolactin in men and non-nursing women, although the increase is greater in women. Oral labetalol does not increase serum prolactin. The maternal prolactin level in a mother with established lactation may not affect her ability to breastfeed. A woman with a history of symptoms of Raynaud's phenomenon developed Raynaud's phenomenon of the nipples when treated for pregnancy-induced hypertension with labetalol 100 mg twice daily. She breastfed for 5 weeks, but nursing caused pain in her nipples. In a subsequent pregnancy, similar symptoms occurred during treatment with labetalol 100 mg twice daily. Discontinuing labetalol eliminated the nipple pain in both instances. A pregnant woman was treated on two occasions with intravenous labetalol for pre-eclampsia. On each occasion, she reported a burning sensation of the nipples. While continuing on labetalol, sustained-release nifedipine was added to her regimen and the burning of the nipple did not return.
References	[1]. Expert Opin Drug Saf . 2015 Mar;14(3):453-61.
Additional Infomation	Labetalol hydrochloride is a member of salicylamides. Labetalol Hydrochloride is the hydrochloride form of labetalol, a third generation selective alpha-1-adrenergic antagonist and non-selective beta-adrenergic antagonist with vasodilatory and antihypertensive properties. Labetalol competitively binds to alpha-1-adrenergic receptors in vascular smooth muscle, thereby inhibiting the adrenergic stimulation of endothelial cell function and vasoconstriction in peripheral blood vessels. This agent also binds to beta-receptors in the bronchial and vascular smooth muscle, resulting in a decrease in adrenergic stimulation. The result is a decrease in resting and exercise heart rates, cardiac output, and in both systolic and diastolic blood pressure, thereby resulting in vasodilation, and negative chronotropic and inotropic cardiac effects. A salicylamide derivative that is a non-cardioselective blocker of BETA-ADRENERGIC RECEPTORS and ALPHA-1 ADRENERGIC RECEPTORS. See also: Labetalol (has active moiety); Hydrochlorothiazide; labetalol hydrochloride (component of).

Solubility Data

Solubility (In Vitro)

DMSO: ≥ 38 mg/mL (~104.2 mM) Water: ~8 mg/mL Ethanol: ~7 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.85 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.85 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.85 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7407 mL	13.7035 mL	27.4070 mL
	5 mM	0.5481 mL	2.7407 mL	5.4814 mL
	10 mM	0.2741 mL	1.3704 mL	2.7407 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.