COMPARISON OF BETA-ADRENERGIC BLOCKING EFFECT OF DCI, METHOXAMINE, PROPRANOLOL, MJ 1999, H 56/28, LB 46 AND I.C.I. 50 172 ON THE CHRONOTROPIC RESPONSE TO ISOPRENALINE

Abstract

In 1958, Powell and Slater (1) first described that DCI had beta-adrenergic blocking activity even though it included beta-adrenergic stimulations. Such property was found also in methoxamine besides its alpha-adrenergic stimulant activity (2, 3). In the following decade, many beta-adrenergic blocking agents have been synthesized successively (4-8) and one of them, propranolol was first introduced in the clinical medicine. Since Ahlquist classified alpha and beta-adrenergic receptors, it has been well established that positive chronotropic and inotropic effects and vaso and broncho-dilator actions of catecholamines are mediated through an interaction between drug and beta-receptor. However, it is not gotten clear, whether all beta-adrenergic blocking agents would have the same potency to block beta-adrenergic receptor in different organs.
In many experiments, the blockade of the positive chronotropic response to catecholamines has been chosen in order to evaluate the potency of beta-adrenergic blocking agents. Excised preparation of atria (3, 9) and also whole animals (5, 7) were used, while drug was added in the bath or given intravenously. James and Nadeau (10) examined the effect of DCI on the sinoatrial pacemaker activity when it was given selectively into the sinus node artery. In this paper we compared the effect of beta-adrenergic blocking activity of DCI (1), methoxamine (2), propranolol (4), MJ 1999 (5), H 56/28 (6), LB 46 (7) and I.C.I. 50 172 (8) selectively administered into the sinus node artery, while isoprenaline was used as an agonist.