Summary . L7810 (4‐carbamoyloxy‐1‐(4‐(4‐fluorophenyl)‐4‐oxobutyl) decahydroquinoline, has a local anaesthetic action on frog nerve 1·75 times that of procaine. . L7810 protected anaesthetized guinea‐pigs against ouabain‐induced ventricular fibrillation and increased the lethal dose of ouabain. . L7810 reduced the rate of rise of intracellularly recorded action potentials in rabbit isolated atria; the resting potential was not affected, but the duration of the action potential was prolonged. . Unlike most drugs with local anaesthetic properties L7810 did not depress contractions in isolated atria but increased them. . L7810 reduced the spontaneous frequency, maximum follow frequency and conduction velocity of rabbit isolated atria. . L7810 had no blocking action on the chronotropic or positive inotropic actions of isoprenaline on isolated atrial muscle. . In anaesthetized dogs L7810 caused a small dose‐related bradycardia, and a large dose‐related decrease in peripheral vascular resistance. There was no blockade of the effects of isoprenaline on heart rate or peripheral blood flow.
The authors are in the Departments of Pharmacology and Anesthesiology, Medical College of South Carolina, Charleston, South Carolina. Dr. Bagwell is Advanced Research Fellow of the South Carolina Heart Association. Dr. Woods, recipient of a Research Career Development Award from the National Institutes of Health. This work was supported by grants from the National Heart Institute (HTS-5200, HE-00040–16 and HE-05348–03) and the South Carolina Heart Association.
An attempt has been made to compare quantitatively the relative potencies of various compounds in blocking the effects of isoprenaline on peripheral blood flow and on heart rate. In anaesthetized dogs a cuff flow probe was placed around the descending aorta, and the inferior mesenteric artery was cannulated in a retrograde direction. Two to three-fold increases in peripheral blood flow conductance were produced by intra-arterial injections of isoprenaline so small that they had little effect on heart rate. Effects of larger intravenous doses of isoprenaline on heart rate were then measured, so that dose response curves for the peripheral and cardiac effects of isoprenaline were obtained in the same dog. Practolol blocked peripheral β-receptors to some extent, but was eight times more potent on the heart. Transference of the acetamide substituent from the para to the ortho position on the ring led to a loss of cardiospecificity. Conversely, the para-substituted isomer of oxprenolol was totally cardiospecific. It had the same potency as oxprenolol on the heart, but did not block the effects of isoprenaline on blood flow at all. Oxprenolol itself, and propranolol, were more potent in blocking peripheral than cardiac β-receptors.
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