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 follow ing 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 cate cholamines are mediated through an interaction between drug and beta-receptor. How ever, 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 cate cholamines 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 isopre naline was used as an agonist. METHODSThirty-seven mongrel dogs, of both sexes, weighing 11 to 18 kg were used. Animals were anesthetized with sodium pentobarbital, 30 mg/kg, intravenously. A tracheal tube was inserted and the artificial respiration was performed by a Bird respirator "mark 8" with room air. The heart was usually exposed through an intercostal incision at the right fourth intercostal space. The pericardium was opened and the heart was kept its original position by making a pericardial cardle. Both vagus nerves were cut at the mid

Effects of Several β-Blockers On Blood Pressure in the Rat

“…The magnitude of the rise elicited by these i3-blocking agents and the minimum doses of these agents required to cause the pressor action appeared to be related to their E3-blocking activities in the heart such as was also reported by several investigators (24)(25)(26)(27). Therefore, the magnitude of the rise and the minimum dose of these agents could be used to compare the relative ( blocking activity of these agents.…”

CARDIOVASCULAR STUDIES OF 5-(3-Tert-Butylamino-2-Hydroxy) PROPOXY-3,4-DIHYDROCARBOSTYRIL HYDROCHLORIDE (OPC- IOS5), a NEW POTENT Β-Adrenergic BLOCKING AGENT

“…Thus we conclude that OPC-1085 has a sympathomime tic action which is well known with alprenolol (18,19), Ko 1366 (10) and dichloroisopro terenol (20). Hashimoto et al (21) and Ohkuda et al (22) have observed that an intra arterial injection of a smaller dose of dichloroisoproterenol, pindolol, alprenolol or pra ctolol produced a positive chronotropic response in the in situ sino-atrial node prepara tion which is the same as was seen with Kb 1366, pindolol or practolol in the isolated blo od-perfused one (23). OPC-1085 induced a more prominent sympathomimetic effect with cumulative administration of increasing doses than did pindolol.…”