Zusammenfassung
Die wichtigsten pharmakologischen Befunde, die zur Klassifizierung der adrenergen α- und β-Receptoren geführt haben, werden besprochen. Hemmstoffe der α-Receptoren werden bereits seit längerer Zeit zu therapeutischen Zwecken verwandt. Ausführlicher werden die Hemmstoffe der β-Receptoren behandelt, die erst in den letzten Jahren Eingang in die Klinik gefunden haben. Die pharmakologischen Wirkungen, Nebenwirkungen und therapeutischen Indikationen der Receptorenhemmstoffe werden besprochen.
Summary
The pharmacological evidence for the classification of adrenergic α- and β-receptors is presented. Drugs blocking α-receptors have been used therapeutically for many years. β-adreneric receptor blocking agents were introduced only recently; they are discussed in more detail. The pharmacological actions, side effects and therapeutic uses of the receptor blocking drugs are summarized.
Literatur
Ahlquist, R. P.: A study of the adrenotropic receptors. Amer. J. Physiol.153, 586 (1948).
Ahlquist, R. P., andB. Levy: Adrenergic receptive mechanism of canine ileum. J. Pharmacol. exp. Ther.127, 146 (1959).
Alleyne, G. A. O. et al.: Effect of pronethalol in angina pectoris. Brit. med. J.1963 II, 1226.
Antonis, A., M. L. Clark, R. L. Hodge, M. Molony, andT. R. E. Pilkington: Receptor mechanisms in the hyperglycaemie response to adrenaline in man. Lancet1967 I, 1135.
Aviado, D. M., andC. F. Schmidt: Effects of sympathomimetic drugs on pulmonary circulation: With special reference to a new pulmonary vasodilator. J. Pharmacol. exp. Ther.120, 512 (1957).
Balcon, R., D. E. Jewitt, J. P. H. Davies, andS. Oram: A controlled trial of propranolol in acute myocardial infarction. Lancet1966 II, 917.
Bath, J. C. J. L., et al.: Propranolol acute myocardial infarction. A multicentre trial. Lancet1966 II, 1435.
Besterman, E. M. M., andD. H. Friedlander: Clinical experiences with propranolol. Postgrad. med. J.41, 526 (1965).
Black, J. W., W. A. M. Duncan, andR. G. Shanks: Comparison of some properties of pronethalol and propranolol. Brit. J. Pharmacol.25, 577 (1965).
Black, J. W., andJ. S. Stephenson: Pharmacology of a new adrenergic beta-receptor-blocking compound (Nethalide). Lancet1962 II, 311.
Blinks, J. R.: The nature of the antagonism by methoxamine of the chronotropic and inotropic effects of catecholamines. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.248, 73 (1964).
Bollinger, A.: Therapie des hyperkinetischen Herzsyndroms. Dtsch. med. Wschr.92, 1399 (1967).
Braunwald, E., andL. S. Cohen: Amelioration of exercise induced angina pectoris in idiopathic hypertrophic subaortic stenosis with beta-adrenergic blockade. Circulation34 (Suppl. 3), 64 (1966).
Castro de la Mata, R., M. Penna, andD. M. Aviado: Reversal of sympathomimetic bronchodilation by dichloro-isoproterenol. J. Pharmacol. exp. Ther.135, 197 (1962).
Cherian, G., J. F. Brockington, P. M. Shah, C. M. Oakley, andI. F. Goodwin: Beta-adrenergic blockade in hypertrophic obstructive cardiomyopathy. Brit. med. J.1966 I, 895.
Clausen, J., M. Felsby, F. Schønan Jørgensen, B. Lyager Nielsen, J. Roin, andB. Strange: Absence of prophylactic effect of propranolol in myocardial infarction. Lancet1966 II, 920.
Clegg, P. C.: The effect of adrenergic blocking agents on the guinea-pig uterus in vitro, and a study of the histology of the intrinsic myometrial nerves. J. Physiol. (Lond.)169, 73 (1963).
Cumming, G. R., andW. Carr: Hemodynamic response to exercise after propranolol in normal subjects. Canad. J. Physiol. Pharmacol.44, 465 (1966a);
Relief of dyspnoeic attacks in Fallot's tetralogy with propranolol. Lancet1966 I, 519.
Cutts, F. B., andB. Rapoport: The routine use of quinidine in acute myocardial infarction. New Engl. J. Med.247, 81 (1952).
Dale, H. H.: On some physiological actions of ergot. J. Physiol. (Lond.)34, 163 (1906).
Dornhorst, A. C., andB. F. Robinson: Clinical pharmacology of a beta-adrenergic blocking agent (Nethalide). Lancet1962 II, 314.
Doutheil, U., H. G. Ten Bruggencate u.K. Kramer: Coronarvasomotorik unter L-Noradrenalin und Isopropylnoradrenalin nach Blockierung der adrenergischenβ-Receptoren durch Nethalide. Pflügers Arch. ges. Physiol.281, 181 (1964).
Epstein, S. E., andE. Braunwald: Beta-adrenergic receptor blocking drugs. Mechanisms of action and clinical applications. New Engl. J. Med.275, 1106, 1175 (1966).
Epstein, S. E., B. F. Robinson, R. L. Kahler, andE. Braunwald: Effects of beta-adrenergic blockade on the cardiac response to maximal and submaximal exercise in man. J. clin. Invest.44, 1745 (1965).
Folkow, B.: Effects of catecholamines on consecutive vascular sections. In: Adrenergic mechanisms. p. 190. London: J. & A. Churchill Ltd. 1960.
Folle, L. E., andD. M. Aviado: Cardiovascular effects of anoxia and the influence of a new beta adrenergic receptor blocking drug. J. Pharmacol. exp. Ther.149, 79 (1965).
Furchgott, R. F.: The receptors for epinephrine and norepinephrine (adrenergic receptors). Pharmacol. Rev.11, 429 (1959);
Receptors for sympathomimetic amines. In: Adrenergic mechanisms, p. 246. London: J. & A. Churchill Ltd. 1960.
Gebhardt, W., H. Reindell, K. König u.Chr. Büchner: Herz- und Kreislaufdynamik nach medikamentöser Beta-Rezeptoren-Blockade. Verh. dtsch. Ges. Kreisl.-Forsch.31, 99 (1965).
Gillam, P. M. S., andP. N. C. Prichard: Use of propranol in angina pectrois. Birt. med. J.1965 II, 337.
Propranolol in the therapy of angina pectoris. Amer. J. Cardiol.18, 366 (1966).
Grant, R. H. E. et al.: Multicenter trial of propranolol in angina pectoris. Amer. J. Cardiol.18, 361 (1966).
Groat, W. C. de, andR. L. Volle: Interactions between the catecholamines and ganglion stimulating agents in sympathetic ganglia. J. Pharmacol. exp. Ther.154, 200 (1966).
Hähnel, L.: Wirkungsnachweis einer Beta-Receptoren blockierenden Substanz am Verhalten einiger Kreislaufwerte. Z. Kreisl.-Forsch.55, 1023 (1966).
Hamer, J., T. Grandjean, C. Melendez, andG. E. Sowton: Effect of propranolol in angina pectoris: Preliminary report. Brit. med. J.1964 II, 720.
Harris, A.: Long term treatment of paroxysmal cardiac arrhythmias with propranolol. Amer. J. Cardiol.18, 431 (1966).
Harris, W. S., C. D. Schoenfeld, R. H. Brooks, andA. M. Weissler: Reversal of epinephrine effects in the human by beta-adrenergic blockade. Clin. Res.12, 337 (1964).
Harrison, D. C., E. Braunwald, G. Glick, D. T. Mason, C. A. Chidsey, andJ. Ross: Effects of beta-adrenergic blockade on circulation, with particular reference to observations in patients with hypertrophic subaortic stenosis. Circulation29, 84 (1964).
Harrison, D. C., andJ. R. Griffin: Metabolic and circulatory responses to selective adrenergic stimulation and blockade. Circulation34, 218 (1966).
Harrison, D. C., J. R. Griffin, andT. J. Fiene: Effects of beta-adrenergic blockade with propranolol in patients with atrial arrhythmias. New Engl. J. Med.273, 410 (1965).
Hegglin, R., H. P. Krayenbühl u.E. Lüthy: Der Einfluß einesβ-Rezeptorenblockers (Nethalide) auf einige Parameter der Kreislaufdynamik. Z. ges. exp. Med.138, 141 (1964).
Hellewell, J., andM. W. Potts: Propranolol and ventricular arrhythmias with halothane. Anaesthesia20, 269 (1965).
Hess, H.: Zur Diagnostik und Behandlung obliterierender Gefäßerkrankungen der unteren Extremität. Dtsch. med. Wschr.81, 1308 und 1323 (1956).
Holtz, P., u.D. Palm: Brenzkatechinamine und andere sympathicomimetische Amine. Biosynthese und Inaktivierung, Freisetzung und Wirkung. Ergebn. Physiol.58, 328ff. (1966).
Honey, M., D. A. Chamberlain, andJ. Howard: Effect of beta-sympathetic blockade on arterial oxygen saturation in Fallot's tetralogy. Circulation30, 501 (1964).
Howe, R., undR. G. Shanks: Optical isomers of propranolol. Nature (Lond.)210, 1336 (1966).
Hunscha, H., M. Kaltenbach u.W. Schellhorn: Zur Therapie der Angina pectoris. Objektive Prüfung von Medikamentenwirkungen mit Hilfe von Arbeitsversuchen. Therapiewoche16, 1153 (1966).
Hynie, S., M. Wenke u.E. Mühlbachová: Zur Charakteristik der Beeinflussung des Glycid-Metabolismus durch Adrenomimetica. Arzneimittel-Forsch.11, 858 (1961).
Iwatsuki, K., T. Yusa, Y. Hashimoto, andY. Watabe: Effect of propranolol on paroxysmal ventricular fibrillation. Tohoku J. exp. Med.88, 257 (1966).
Johnstone, M.: Beta adrenergic blockade with Inderal (Propranolol) during anaesthesia. Anaesthesist15, 96 (1966).
Keelan, P.: Double-blind trial of propranolol (Inderal) in angina pectoris. Brit. med. J.1965 I, 897.
Kotler, M. N., L. Berman, andA. H. Rubenstein: Hypoglycemia precipitated by propranolol. Lancet1966 II, 1389.
Kukovetz, W. R., u.G. Pöch: Die Hemmung mechanischer und metabolischer Ketecholaminwirkungen durch Isopropylmethoxamin und Kö 592 am Herzen. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path.256, 310 (1967).
Kuschinsky, G., u.K. H. Rahn: Untersuchungen über die Beziehungen zwischen chinindinartigen undβ-adrenolytischen Wirkungen von 1-(3-Methylphenoxy)-2-hydroxy-3-isopropyl-aminopropan (Kö 592). Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.252, 50 (1965).
Lands, A. M., A. Arnold, J. P. McAuliff, F. P. Luduena, andT. G. Brown jr. Differentiation of receptor systems activated by sympathomimetic amines. Nature (Lond.)214, 597 (1967).
Lands, A. M., andT. G. Brown jr.: Comparison of the cardiac stimulating and bronchodilator actions of selected sympathomimetic amines. Proc. Soc. exp. Biol. (N. Y.)116, 331 (1964).
Langley, J. N.: On the reaction of cells and of nerve-endings to certain poisons, chiefly as regards the reaction of striated muscle to nicotine and to curari. J. Physiol. (Lond.)33, 374 (1905).
Levy, B., andR. P. Ahlquist: Adrenergic drugs. In:Drill's pharmacology in medicine (ed.:J. R. Di Palma), p. 463. New York: McGraw-Hill Book Co., 1965.
Levy, J. V., andV. Richards: Inotropic and chronotropic effects of a series ofβ-adrenergic blocking drugs: Some structure-activity relationships. Proc. Soc. exp. Biol. (N. Y.)122, 373 (1966).
Levy, B., andS. Tozzi: The adrenergic receptive mechanism of the rat uterus. J. Pharmacol. exp. Ther.142, 178 (1963).
Lucchesi, B. R.: The actionof nethalide upon experimentally induced cardiac arrhythmias. J. Pharmacol. exp. Ther.145, 286 (1964).
Lucchesi, B. R., andH. F. Hardman: The influence of dichlorisoproterenol (DCI) and related compounds upon ouabain and acethylstrophanthidin induced cardiac arrhythmias. J. Pharmacol. exp. Ther.132, 372 (1961).
Maxwell, R. A.: Adrenergic blocking drugs and adrenergic neuron blocking drugs. In:Drill's Pharmacology in medicine (ed.:J. R. Di Palma), p. 502. New York: Mc Graw-Hill Book Co. 1965.
Maxwell, G. M., E. Robertson, andR. B. Elliot: The effect of a new beta-adrenergic blocking agent (nethalide; Alderlin) upon the general and coronary haemodynamics of the intact animal. Austral. J. exp. Biol. med. Sci.41, 511 (1963).
McKenna, D. H., R. J. Corliss, S. Sialer, W. C. Zarnstoff, Ch. W. Crumpton, andG. W. Rowe: Effect of propranolol on systemic and coronary hemodynamics at rest and during simulated exercise. Circulat. Res.19, 520 (1966).
McNeill, R. S.: Effect of aβ-adrenergic-blocking agent, propranolol, on asthmatics. Lancet,1964 II, 1101.
Mc Neill, R. S., andCh. G. Ingram: Effect of propranolol on ventilatory function. Amer. J. Cardiol.18, 473 (1966).
Meier, M., P. Hedwall u.H. Brunner: Wirkungen von Hydralazin und Propranolol auf Coronardurchblutung und Sauerstoffverbrauch des Myokard. Helv. physiol. pharmakol. Acta23, C36 (1965).
Meier, J., H. Lydtin u.N. Zöllner: Über die Wirkung von adrenergenβ-Receptorenblockern auf ventilatorische Funktionen bei obstruktiven Lungenkrankheiten. Dtsch. med. Wschr.91, 145 (1966).
Moran, N. C., J. I. Moore, A. K. Holcomb, andG. Mushet: Antagonism of adrenergically induced cardiac arrhythmias by dichlorisoproterenol. J. Pharmacol. exp. Ther.136, 327 (1962).
Moran, N. C., andM. E. Perkins: Adrenergic blockade of the mammalian heart by a dichloro analogue of isoproterenol. J. Pharmacol. exp. Ther.124, 223 (1958).
Muir, G. G., D. A. Chamberlain, andD. Turnstall Pedoe: Effects ofβ-sympathetic blockade on non-esterified-fatty-acid and carbohydrate metabolism at rest and during exercise. Lancet1964 II, 930.
Nickerson, M.: The pharmacology of adrenergic blockade. Pharmacol. Rev.1, 27 (1949);
Die medikamentöse Behandlung des Schocks. In: Schock. Pathogenese und Therapie, S. 398 (Hrsg.K. D. Bock). Berlin-Göttingen-Heidelberg: Springer 1962.
Nickerson, M., andC. M. Chan: Blockade of responses of isolated myocardium to epinephrine. J. Pharmacol. exp. Ther.133, 186 (1961).
Paget, G. E.: Carcinogenic action of pronethalol. Brit. med. J.1963 II, 1266.
Parratt, J. R.: Blockade of sympatheticβ-receptors in the myocardial circulation. Brit. J. Pharmacol.24, 601 (1965).
Parratt, J. R., andJ. Grayson: Myocardial vascular reactivity after beta-adrenergic blockade. Lancet1966 I, 338.
Paulk, E. A., andJ. W. Hurst: Clinical problems of cardioversion. Amer. Heart J.70, 248 (1965).
Pilkington, T. R. E., R. D. Lowe, B. F. Robinson, andE. Titterington: Effect of adrenergic blockade on glucose and fatty-acid mobilisation in man. Lancet1962 II, 316.
Powell, C. E., andI. H. Slater: Blocking of inhibitory adrenergic receptors by a dichloro analog of isoproterenol. J. Pharmacol. exp. Ther.122, 480 (1958).
Prichard, B. N. C.: Hypotensive action of pronethalol. Brit. med. J.1964 I, 1227.
Prichard, B. N. C., andP. M. S. Gillam: Use of propranolol (Inderal) in treatment of hypertension. Brit. med. J.1964 II, 725;
Propranolol in hypertension. Amer. J. Cardiol.18, 387 (1966).
Rabkin, R., D. P. Stables, N. W. Levin, andM. M. Suzman: The prophylactic value of propranolol in angina pectoris. Amer. J. Cardiol.18, 370 (1966).
Rahn, K. H., u.Th. Ockenga: Über die Beziehungen zwischen denβ-adrenolytischen Wirkungen und dem Einfluß auf Herzfrequenz und Herzminutenvolumen vonβ-Receptoren blok-kierenden Substanzen. Klin. Wschr. (im Druck).
Richards, F. A.: Propranolol in hypertension. Amer. J. Cardiol.18, 384 (1966).
Ross, S. B.: Effect of various compounds on adrenergic mechanisms recorded by changes in heart rates of anaesthetized mice. Acta pharmacol. (Kbh.)20, 253 (1963).
Ross, E. J., B. N. C. Prichard, L. Kaufman, A. I. G. Robertson, andB. J. Harris: Preoperative and operative management of patients with pheochromocytoma. Brit. med. J.1967 I, 191.
Rossum, J. M. van: Different types of sympathomimetic α-receptors. J. Pharm. Pharmacol.17, 202 (1965).
Rowlands, D. J., G. Howitt, andP. Markman: Propranolol (Inderal) in disturbances of cardiac rhythm. Brit. med. J.1965 I, 891.
Schaepdryver, A. F. de: Fluorometric estimation of adrenaline and noradrenaline in urine and blood and diagnosis of chromaffin cell tumors. Arch. int. Pharmacodyn.121, 489 (1959).
Schamroth, L.: Immediate effects of intravenous propranolol on various cardiac arrhythmias. Amer. J. Cardiol.18, 438 (1966).
Schmid, E.: Untersuchungen über Physiologie und Pathophysiologie des sympathikoadrenalen Systems durch Bestimmung der Vanillin-Mandelsäure-Ausscheidung im Harn mit dünnschichtchromatographischer Technik. Arch. Kreisl.-Forsch.49, 83 (1966).
Schröder, G., andL. Werkö: Hemodynamic studies and clinical experience with nethalide, a beta-adrenergic blocking agent. Amer. J. Cardiol.15, 58 (1965).
Schümann, H. J.: Die biochemische Diagnose des Phäochromozytoms. Dtsch. med. Wschr.86, 2016 (1961).
Sekiya, A., andE. M. Vaughan Williams: A comparison of the antifibrillatory actions and effects on intracellular cardiac potentials of pronethalol, Disopyramide and quinidine. Brit. J. Pharmacol.21, 473 (1963).
Shanks, R. G.: Methods for the evaluation of adrenergic beta-receptor antagonits. Methods in drug evaluation, ed. byP. Mantegazza andF. Piccinini, p. 183. Amsterdam: North-Holland Publ. Co. 1966.
Sloman, G., J. S. Robinson, andK. McLean: Propranolol (Inderal) in persistent ventricular fibrillation. Brit. med. J.1965 I, 895.
Smith, C. B.: Relaxation of the nictitating membrane of the spinal cat by sympathomimetic amines. J. Pharmacol. exp. Ther.142, 163 (1963).
Snow, P. J. D.: Treatment of acute myocardial infarction with propranolol. Amer. J. Cardiol.18, 458 (1966).
Somani, P., andB. K. B. Lum: The antiarrhythmic actions of beta adrenergic blocking agents. J. Pharmacol. exp. Ther.147, 194 (1965).
Sowton, E., andJ. Hamer: Hemodynamic changes after beta adrenergic blockade. Amer. J. Cardiol.18, 317 (1966).
Srivastava, S. C., H. A. Dewar, andD. J. Newell: Double-blind trial of propranolol (Inderal) in angina of effort. Brit. med. J.1964 II, 724.
Stephen, St. A.: Unwanted effects of propranolol. Amer. J. Cardiol.18, 463 (1966).
Stock, J. P. P. Beta adrenergic blocking drugs in the clinical management of cardiac arrhythmias. Amer. J. Cardiol.18, 444 (1966).
Stock, J. P. P., andN. Dale: Beta-adrenergic receptor blockade in cardiac arrhythmias. Brit. med. J.1963 II, 1230.
Strubelt, O.: Die kalorigene und positiv chronotrope Wirkung sympathicomimetischer Amine und ihre Beeinflussung durch Blockade der adrenergischenβ-Rezeptoren. Arzneimittel-Forsch.16, 587 (1966).
Tanz, R. D.: The action of ouabain on cardiac muscle treated with reserpine and dichloroisoproterenol. J. Pharmacol. exp. Ther.144, 205 (1964).
Taylor, R. R., C. J. Johnston, andA. D. Jose: Reversal of digitalis intoxication by beta-adrenergic blockade with pronethalol. New Engl. J. Med.271, 877 (1964).
Tsolakas, T. C., J. P. H. Davies, andS. Oram: Propranolol in attempted maintenance of sinus rhythmus after electrical defibrillation. Lancet1964 II, 1064.
Tucker, M. J., S. J. Alcock, and S. B.de Baker: Absence of carcinogenic properties of propranolol in mice. Brit. med. J.1965 II, 363.
Turner, J. R. B.: Propranolol in the treatment of digitalis-induced and digitalis-resistant tachycardias. Amer. J. Cardiol.18, 450 (1966).
Vogel, J. H. K., andS. G. Blount jr.: Modification of cardiovascular responses by propranolol. Brit. Heart J.29, 310 (1967).
Waal, H. J.: Hypotensive action of propranolol. Clin. Pharmacol. Ther.7, 588 (1966).
Warkentin, D. L., andM. R. Valenca: Response of hyperkinetic heart syndrome to beta-adrenergic receptor blockade. Clin. Res.13, 404 (1965).
Winsor, T., andC. Hyman: Clinical pharmacology of vasodilating drugs. Clin. Pharmacol. Ther.2, 636 (1961).
Wislicki, L.: The effect of pronethalol on rabbit auricles and its interactions with sympathomimetic amines. Arch. int. Pharmacodyn.152, 69 (1964).
Wolfson, S., M. V. Herman, J. M. Sullivan, andR. Gorlin: Conversion of atrial fibrillation and flutter by propranolol. Brit. Heart J.29, 305 (1967).
Wolfson, S., S. I. Robbins, andN. Krasnow: Treatment of cardiac arrhythmias with beta-adrenergic blocking agents. Amer. Heart J.72, 177 (1966).
Zaid, G., andG. N. Beall: Bronchial response to beta-adreneric blockade. New Engl. J. Med.275, 580 (1966).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Muscholl, E., Rahn, K.H. Adrenerge α- und β-Receptoren und ihre spezifischen Hemmstoffe. Klin Wochenschr 46, 113–119 (1968). https://doi.org/10.1007/BF01727368
Issue Date:
DOI: https://doi.org/10.1007/BF01727368