Beta-Receptoren-Blocker [antikvár]

1. Foreword M S 1' 'I it! • Raymond P. Ahlquist, Ph. D., F.C.P. Charbonnier Professor, Pharmacology Medical College of Georgia Augusta, Georgia, U.S.A. About thirty years ago we invented the alpha and beta adrenoceptors to t '' 'j explain the different responses obtained with different catecholamines. ^ ' 'i Although this idea went unrecognized for ten years the dual receptor concept gradually attained acceptance. Three postdoctoral students (Levy, Shanks and Lydtin), trained in our laboratory were instrumental in fully developing the concept. The late Dr. Bernard Levy carried out many of the studies that form the basis of our present beliefs about the adrenergic receptor. Briefly these can be summarized as follows: From a pharmacological view point there are two kinds of adrenergic receptors. The alpha adrenoceptor responds speciiically to phenylephrine, responds best to adrenaline and does not respond to isopren- ' aline. The alpha adrenoceptor is associated with vasoconstriction, contraction of the smooth muscle of the iris dilator (mydriasis), spleen capsule and myometrium, and relaxation of the gut. The beta adrenoceptor responds specifically to isoprenaline, responds well to adrenaline and does not respond to phenylephrine. The beta adrenoceptor is associated with cardiac stimulation, and relaxation of the smooth muscle of blood vessels, bronchi, myometrium and gut. At the time of the original publication of this dual receptor concept (1948) blocking agents for the alpha adrenoceptor were well known. Although unknown at the time all of the effects of a beta adrenoceptor blocking agent were completely predictable. It was not until 1958 that the first beta adrenoceptor blocking agent was described by Moran and Perkins. This was dichloroisoprenaline (DCI). Professor Robin Shanks, now of Belfast, following his stay in this laboratory, joined Imperial Chemical Industries (I.C.I.). He was the first to administer DCI to a human. In 1962 Professor James Black, then at I.C.I., now at London, proposed pronethalol as a treatment for angina pectoris. This was followed by propranolol, since pronethalol turned out to be carcinogenic in mice. Professor Shanks has been involved in many of the basic and clinical studies of propranolol, practolol, atenolol, and other beta blockers. As stated above the receptors were first described in terms of agonist response: phenylephrine acts specifically on alpha adrenoceptors, isoprenaline on beta. Now it is possible to complete the delineation using the specific blocking agents. The alpha adrenoceptor is competitively blocked by phentolamine. This drug blocks all of the responses to phenylephrine, part of the responses to adrenaline, and does not significantly modify the responses to isoprenaline. The beta adrenoceptor is specifically blocked by propranolol : ;