Summary
Labetalol, a combined α-β-adrenergic antagonist, is one of the new group of β-adrenergic blockers reduces peripheral and coronary vascular resistances while preserving cardiac output. Unlike α-adrenergic blockers, labetalol tends to reduce heart rate during rest and exercise. The drug is a potent antihypertensive agent which has been used by mouth and by vein to treat mild, moderate, and severe hypertension, including hypertensive emergencies. Labetalol has a hemodynamic profile which makes it an attractive agent for treating myocardial ischemia. The drug reduces blood pressure, left ventricular wall tension, heart rate, and contractility while preserving or even augmenting coronary blood flow. Studies with labetalol in hypertensive patients with angina have shown it to be more effective than placebo in reducing angina attacks and blood pressure while improving exercise tolerance. The drug appears to have antianginal and antihypertensive effects comparable to atenolol and propranolol. Side effects of treatment are observed and most are related to α- and β-adrenergic blockade. Labetalol also appears to be effective for treatment of normotensive patients with angina and for silent myocardial ischemia. It has no apparent effects on serum lipids and lipoproteins. Labetalol appears to be a useful drug for treating the hypertensive heart and its many complications.
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Frishman W, Halprin S. Clinical pharmacology of the new beta-adrenergic blocking drugs. Part 7. New horizons in beta-adrenoceptor blockade therapy: Labetalol. Am Heart J 1979; 98:660–665.
Farmer JB, Kennedy I, Levy GP, Marshall RJ: Pharmacology of AH5158: A drug which blocks both α- and β-adrenoceptor blocking drugs. Br J Clin Pharmacol 1972; 45:660–675.
Wallin JD, O'Neill WM: Labetalol. Arch Intern Med 1983; 143:485–490.
Frishman WH, Strom JA, Kirschner M, et al. Labetalol therapy in patients with systemic hypertension and angina pectoris: Effects of combined alpha and beta-adrenoceptor blockade. Am J Cardiol 1981; 48:917–927.
MacCarthy EP, Bloomfield SS. Labetalol: A review of ita pharmacology, pharmacokinetic elinical uses and side effects. Pharmacotherapy 1983; 3:193–219.
Brittain RT, Drew GM, Levy GP. The α- and β-adrenoceptor blocking potencies of labetalol and its individual stereoisomers in anesthetized dogs and in isolated tissues. Br J Pharmacol 1982; 77:105–114.
Aggerbeck M, Guellaen G, Hanoune J. N-alkyl substitution increases the affinity of adrenergic drugs for the α-adrenoceptor in rat liver. Br J Pharmacol 1979; 65:15–22.
Brittain RT, Levy GP. A review of the animal pharmacology of labetalol, a combined α- and β-adrenoceptor blocking drug. Br J Clin Pharmacol 1976; 3 (Suppl 3):681–694.
Blakeley AG, Summers RJ. The pharmacology of labetalol, an α- and β-adrenoceptor blocking agent. Gen Pharmacol 1978; 9:399–402.
Baum T, Sybertz EJ. Pharmacology of labetalol in experimental animals. Am J Med 1983; 75 (4A):15.
Carey B, Whalley ET. Labetalol possesses β-adrenoceptor agonist action on the isolated rat uterus. J Pharm Pharmacol 1979; 31:791–792.
Carey B, Whalley ET. β-adrenoceptor agonist activity of labetalol on the isolated rat uterus. Br J Pharmacol 1979; 67:13–15.
Carpenter JR. Intrinsic activity of labetalol on guinea pig isolated trachea. J Pharm Pharmacol 1981; 33:806–807.
Johnson GL, Prioli NA, Ehrreich SJ. Antihypertensive effects of labetalol (SCH 15719W, AH5158A) (abstr). Fed Proc 1977; 36:1049–1053.
Dage RC, Hsieh CP. Direct vasodilatation by labetalol in anesthetized dogs. Br J Pharmacol 1980; 70:287–293.
Sybertz EJ, Sabin CS, Pula KK, et al. Alpha and beta-adrenoceptor blocking properties of labetalol and its R-R-isomer, SCH 19927. J Pharmacol Exp Ther 1981; 218:435–442.
Katano Y, Takeda K, Nakagawa Y, et al. α- and β-adrenoceptor blocking actions of labetalol and effects on the myocardial function, coronary circulation and myocardial energy metabolism thereof. Folia Pharmacol Jpn 1978; 74:819–832.
Blakeley AG, Summars RJ. The effects of labetalol (AH5158) on adrenergic transmission in the cat spleen. Br J Pharmacol 1977; 59:643–650.
Levy GP, Richards DA. Labetalol In: Scriabine A, ed. Pharmacology of Antihypertensive Agents. New York: Raven Press, 1980; 325–347.
Hoffman BB, Lefkowitz R. Alpha-adrenergic receptor subtypes. N Engl J Med 1982; 302:1390–1397.
Boakes AJ, Knight EJ, Prichard BNC. Preliminary studies of the pharmacologic effects of 5–1-hydroxy-2-(1-methyl-3 phenylpropyl) amino ethyl salicyolamide (AH 5158) in man. Clin Sci 1971; 40:188–192.
Richards DA. Pharmacologic effects of labetalol in man. Br J Clin Pharmacol 1976; 3(Suppl 3):721–773.
Richards DA, Prichard BNC, Dobbs RJ. Adrenoceptor blockade of the circulatory responses to intravenous isoproterenol. Clin Pharmacol Ther 1978; 24:264–273.
Richards DA, Woodings EP, Stephen MDB, et al. The effects of oral AH5158, a combined α- and β-adrenoceptor antagonist in healthy volunteers. Br J Clin Pharmacol 1974; 1:505–509.
Richards DA, Prichard BNC, Boakes AJ, et al. Pharmacological basis for antihypertensive effects of intravenous labetalol. Br Heart J 1977; 39:99–106.
Richards DA, Prichard BNC, Hernandez R. Circulatory effects of noreadrenaline and adrenaline befor and after labetalol. Br J Clin Pharmacol 1979; 7:371–378.
Richards DA, Tuckman J, Prichard BNC. Assessment of alpha and beta-adrenoceptor blocking action of labetalol. Br J Clin Pharmacol 1976; 3:849–855.
Maconochie JG, Richards DA, Woodings EP. Modification of pressor responses induced by “cold” (abstr). Br J Clin Pharmacol 1977; 4:389–394P.
Richards DA, Maconochie JG, Bland RE, et al. Relationship between plasma concentrations and pharmacological effects of labetalol. Eur J Clin Pharmacol 1977; 11:85–90.
Mehta J, Cohn JN. Hemodynamic effects of labetalol, an alpha and beta adrenergic blocking agent, in hypertensive subjects. Circulation 1977; 55:370–375.
Baum T, Watkins B, Sybertz Z, et al. Antihypertensive and hemodynamic actions of SCH 19927, the R-R isomer of labetalol. J Pharmacol Exp Ther 1981; 218:444–457.
Majid PA, Meeran MK, Benaim ME, et al. α- and β-Adrenoceptor blockade in the treatment of hypertension. Br Heart J 1974; 36:588–594.
Maxwell GM. The effects of a new alpha and beta-adrenoceptor antagonist (AH 51581) upon the general and coronary hemodynamics of intact dogs. Br J Clin Pharmacol 1973; 49:370–372.
Chen DG, Dai X-Z, Zimmerman BG, Bache RJ. Postsynaptic α1-and β2-adrenergic mechanisms in coronary vasoconstriction. J Cardiovasc Pharmacol 1988; 11:61–68.
Brittain RT, Harris DM, Jack D, et al. Labetalol. In: Goldberg ME, ed. Pharmacological and biochemical properties of drug substances. Am Pharm Assoc Acad Pharm Sci 1979:229–254.
Drew GM, Hilditch A, Levy GP. The relationships between the cardiovascular effects, α- and β-adrenoceptor blocking actions and plasma concentration of labetalol in DOCA hypertensive rats. Clin Exp Hypertens 1979; 1:597–611.
Koch G. Hemodynamic changes after acute and long-term combined alpha-beta adrenoceptor blockade with labetalol as compared with beta-receptor blockade. J Cardiovasc Pharmacol 1981; 3(Suppl 1):s30-s41.
Agabiti-Rosei E, Alicandri CL, Beschi M, et al. The acute and chronic hypotensive effect of labetalol and the relationship with pretreatment plasma noradrenaline levels. Br J Clin Pharmacol 1982; 13 (Suppl 1):87s-96s.
Joekes AM, Thompson FD. Acute haemodynamic effects of labetalol and its subsequent use as an oral hypotensive agent. Br J Clin Pharmacol 1976; 3(Suppl 3):789–793.
Koch G. Cardiovascular dynamics after acute and long-term α- and β-adrenoceptor blockade at rest, supine and standing, and during exercise. Br J Clin Pharmacol 1979; 8 (Suppl 2):101s-107s.
Svendsen TL, Rasmussen S, Hartling OJ. Sequential haemodynamic effects of labetalol at rest and during exercise in essential hypertension. Postgrad Med J 1980; 56 (Suppl 2):21–26.
Prichard BNC, Thompson FO, Boakes AJ, et al. Some haemodynamic effects of compound AH 5158 compared with propranolol, propranolol plus hydralazine, and diazoxide: The use of AH 5158 in the treatment of hypertension. Clin Sci Mol Med 1975; 48:97s-102s.
Bahlmann J, Brod J, Hubrich W, et al. Effect of an α- and β-adrenoceptor blocking agent (labetalol) on haemodynamics in hypertension. Br J Clin Pharmacol 1979; 8(Suppl 2):113s-116s.
Trap-Jensen J, Clausen JP, Hartling OJ, et al. Immediate effects of labetalol on central, splanchnic-hepatic, and forearm haemodynamics during pleasant emotional stress in hypertensive patients. Postgrad Med J 1980; 56(Suppl 2):37–46.
Omvik P, Lund-Johansen P. Acute hemodynamic effects of labetalol in severe hypertension. J Cardiovasc Pharmacol 1982; 4:915–919.
Lund-Johansen P. Comparative haemodynamic effects of labetalol, timolol, prazosin and the combination of tolamolol and prazosin. Br J Clin Pharmacol 1979; 8(Suppl 2):107s-114s.
Edwards RC, Raftery EB. Haemodynamic effects of long-term oral labetalol. Br J Clin Pharmacol 1976; 3(Suppl 3):733–740.
Fagard R, Amery A, Reybrouck T, et al. Response of the systemic and pulmonary circulation to alpha and beta-receptor blockade (labetalol) at rest and during exercise in hypertensive patients. Circulation 1979; 60:1214–1219.
Lund-Johansen P. Acute and chronic (six years) hemodynamic effects of labetalol in essential hypertension. Am J Med 1983; 75(4A) (Suppl):24–30.
Gagnon RM, Morissette M, Presant S, et al. Hemodynamic and coronary effects of intravenous labetalol in coronary artery disease. Am J Cardiol 1982; 49:1267–1271.
Prida XE, Hill JA, Feldman RL. Systemic and coronary hemodynamic effects of combined alpha- and beta-adrenergic blockade (labetalol) in normotensive patients with stable angina pectoris and positive exercise stress test responses. Am J Cardiol 1987; 59:1084–1088.
Feldman RL, Prida XE, Lambert CR, Hill JA. Systemic and coronary hemodynamics of labetalol in normotensive patients with ischemic heart disease. Cardiovasc Drugs Ther (in press).
Breckenridge A, Orme M, Serlin MJ, Maciver M. Labetalol in essential hypertension. Br J Pharmacol 1982; 13 (Suppl 1):37s-41s.
Brogden RN, Heel RC, Speight TM, Avery GS. Labetalol: A review of its pharmacology and therapeutic uses in hypertension. Drugs 1978; 15:251–270.
Prichard BNC, Richards DA. Comparison of labetalol with other antihypertensive drugs Br J Clin Pharmacol 1982; 13 (Suppl 1):41s-45s.
Kane JA. Labetalol in general practice. Br J Clin Pharmacol 1982; 13(Suppl 1):59s-62s.
Dargie HJ, Dollery CT, Daniel J. Labetalol in resistant hypertension. Br J Clin Pharmacol 1976; 3(Suppl 3):751–755.
Milne BJ, Logan AG. Labetalol: Potent antihypertensive agent that blocks both αN and β-adrenergic receptors. Can Med Assoc J 1980; 123:1013–1020.
Frick MH, Porsti P. Combined alpha amd beta-adrenoceptor blockade with labetalol in hypertension. Br Med J 1976; 1:1046–1053.
Larochelle P, Hamet P, Hoffman B, et al. LLabetalol in essential hypertension. J Cardiovasc Pharmaco 1980; 2:751–755.
Davidov ME, Moir GD, Poland MP, et al. Monotherapy with labetalol in the treatment of hypertension. A double-blind study. Am J Med 1983; 75(4A) (Suppl):47–53.
Kane J, Gregg I, Richards DA. A double-blind trial of labetalol. Br J Clin Pharmacol 1976; 3(Suppl 3):737–744.
Dawson A, Johnson BF, Smith IK. Comparison of the effects of labetalol, bendrofluazide and their combination in hypertension. Br J Clin Pharmacol 1979; 8:149–154.
Horvath JS, Caterson RJ, Collett P, et al. Labetalol and bendrofluazide: Comparison of their antihypertensive effects. Med J Aust 1979; 1:626–632.
Lifshitz AA, McMahon FG, Jain AK, et al. Combined trichlormethiazide and labetalol therapy in moderate to severe hypertension (abstr). Clin Pharmacol Ther 1978; 23:118–122.
Bloomfield S, Sinkfield A, Bichlmeir G, et al. Labetalol with hydrochlorothiazide for moderate essential hypertension (abstr). Clin Pharmacol Ther 1982; 31:204–208.
Lechi A, Pomari S, Berto R, et al. Clinical evaluation of labetalol alone and combined with chlorthalidone in essential hypertension: A double-blind multicentre controlled study. Eur J Clin Pharmacol 1982; 22:289–294.
Bloomfield SS, Lucas CP, Gantt CL, et al. Step II treatment with labetalol for essential hypertension. Am J Med 1983; 75(4A) (Suppl):81–89.
Michelson EL, Frishman WH, Lewis JE et al. Multicenter clinical evaluation of the long-term efficacy and safety of labetalol in the treatment of hypertension. Am J Med 1983; 75(4A) (Suppl):68–80.
Hunyor SN, Bauer GE, Ross M, Larkin H. Labetalol and propranolol in mild hypertensives: Comparison of blood pressure and plasma volume effects. Aust NZ J Med 1980; 10:162–166.
Prichard BNC, Boakes AJ. Labetalol in long-term treatment of hypertension. Br J Clin Pharmacol 1980; 3 (Suppl 3):743–749.
McNeil JJ, Louis WJ. A double-blind crossover comparison of pindolol, metoprolol, atenolol and labetalol in mild to moderate hypertension. Br J Clin Pharmacol 1979; 8 (Suppl 2):163s-166s.
Romo M, Halttunen P, Saarinen P, Sarna S. Labetalol and pindolol in the treatment of hypertension: A comparative study. Ann Clin Res 1979; 11:249–252.
Pugsley DJ, Nassim M, Armstrong BK, Bellin L. A controlled trial of labetalol (Trandate), propranolol and placebo in the management of mild to moderate hypertension. Br J Clin Pharmacol 1979; 7:63–68.
Kofod P, Kjaer K, Vejlo S, Hvidt S. Labetalol and alprenolol: A comparative investigation of antihypertensive effect. Postgrad Med J 1980; 56 (Suppl 2):69–74.
Bjerle P, Fransson L, Koch G, et al. Pindolol and labetalol in hypertension: Comparison of their antihypertensive effects with particular respect to conditions in the upright posture and during exercise. Curr Ther Res 1980; 27:516–523.
Pugsley DJ, Armstrong BK, Nassim MA, et al. Controlled comparison of labetalol and propranolol in the management of severe hypertension. Br J Clin Pharmacol 1976; 3 (Suppl 3):777–782.
Nicholls DP, Husaini MH, Bulpitt CJ, et al. Comparison of labetalol and propranolol in hypertension. Br J Clin Pharmacol 1980; 9:233–238.
Saunders E, Curry C, Hinds J, et al. Labetalol compared to propranolol in the treatment of black hypertensive patients. J Clin Hypertens 1987; 3:294–337.
Ghose RR, Sampson A. Rapid onset of action of oral labetalol in severe hypertension. Curr Med Res Opin 1977; 5:147–151.
Davies AB, Bala Subramanian V, Gould B, Raftery EB. Rapid reduction of blood pressure with acute oral labetalol. Br J Clin Pharmacol 1982; 13:705–711.
Pearson RM, Griffith DNW, Woollard M, et al. Comparison of effects on cerebral blood flow of rapid reduction in systemic arterial pressure by diazoxide and labetalol in hypertensive patients: Preliminary findings. Br J Clin Pharmacol 1979; 8 (Suppl 2):195s-198s.
Wilson DJ, Wallin JD, Vlachakis ND, et al. Intravenous labetalol in the treatment of severe hypertension and hypertensive emergencies. Am J Med 1983; 75 (4A) (Suppl):95–102.
Frishman WH, Strom JA, Kirschner M, et al. Labetalol therapy in patients with systemic hypertension and angina pectoris: Effects of combined alpha and beta adrenoceptor blockade. Am J Cardiol 1981; 48:917–928.
Frishman W, Charlap S, Kimmel B, et al. Comparison of labetalol to propranolol in patients with both angina pectoris and hypertension: A double-blind study (abstr). J Am Coll Cardiol 1986; 7:27a.
Opie LH. Role of vasodilation in the antihypertensive and antianginal effects of labetalol. Implications for therapy of combined hypertension and angina. Cardiovasc Drugs Ther (in press).
Fox K, Guyyumi AA. Labetalol in normotensive patients with angina pectoris. Cardiovasc Drugs Ther (in press).
Rocco MB, Nobel E, Mead K, et al. Effects of beta vs alpha/beta blockade on transient myocardial ischemia (abstr). Circulation 1987; 76 (Suppl 4):27.
Waal-Manning HJ, Simpson FO. Review of long-term treatment of hypertension with labetalol. Br J Clin Pharmacol 1982; 13 (Suppl 1):65–73.
Takeda T, Kaneko Y, Omae T, et al. The use of labetalol in Japan: Results of multicentre clinical trials. Br J Clin Pharmacol 1982; 13 (Suppl 1):49s-57s.
Kane J, Gregg I, Richards DA. A double-blind trial of labetalol. Br J Clin Pharmacol 1976; (Suppl 3):737–741.
Gange RW, Wilson Jones E. Bullous lichen planus caused by labetalol. Br Med J 1978; 1:816–817.
Finlay AY, Waddington E. Cutaneous reactions to labetalol (letter). Br Med J 1978; 1:987.
Branford WA, Hunter JAA, Muir AL. Cutaneous reaction to labetalol. Practitioner 1978; 221:765–767.
Kristensen BO. Labetalol-induced Peyronie's disease? Acta Med Scand 1979; 206:511–512.
Collier JG, Dawnay NAH, Nachev CH, et al. Clinical investigation of an antagonist at α- and β-adrenoceptors AH 5158A. Br J Pharmacol 1972; 44:286–293.
Andersson O, Berglund G, Hansson L. Antihypertensive action, time of onset and effects on carbohydrate metabolism of labetalol. Br J Clin Pharmacol 1976; 3 (Suppl 3):757–761.
Seedat YK. Labetalol in the treatment of Black and Indian hypertensive patients. Med Proc 1979; 25:53.
Griffiths ID, Richardson J. Lupus-type illness associated with labetelol. Br Med J 1979; 2:496–497.
Stevenson CJ. Antimitochondrial antibodies associated with labetalol (letter). Lancet 1980; 2:924.
Wilson JD, Booth RJ, Bullock JY, Campbell DG. Antimitochondrial antibodies associated with labetalol. Lancet 1980; 2:312–313.
Hachamovitch R, Sonnenblick EH, Strom JA, Frishman WH. Left ventricular hypertrophy in hypertension and the effects of antihypertensive drug therapy. Curr Prob Cardiol 1988; 13:371–421.
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Frishman, W.H. Properties of labetalol, a combined α-and β-blocking agent, relevant to the treatment of myocardial ischemia. Cardiovasc Drug Ther 2, 343–353 (1988). https://doi.org/10.1007/BF00054642
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DOI: https://doi.org/10.1007/BF00054642