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Cardiovascular and Neuromuscular Effects of Three Steroidal Neuromuscular Blocking Drugs in Dogs (ORG 9616, ORG 9426, ORG 9991)

Received from the Department of Anesthesia, University of California, San Francisco, California; the Veterans Administration Medical Center, San Francisco, California; and the Research Group of the Institutes for Experimental Anesthesiology and Clinical Pharmacology, University of Groningen, Groningen, The Netherlands.

Abstract

Developmental research has been directed toward creating nondepolarizing muscle relaxants with an onset time and duration of actions shorter than that of vecuronium or atracurium. We determined the cardiovascular and neuromuscular effects of three new and promising nondepolarizing muscle relaxants in six dogs anesthetized with halothane. Each dog was anesthetized four times (each time separated from the others by at least 1 wk); one muscle relaxant was studied each time. Three doses (one, three, and five times the ED₉₀) were given as intravenous bolus injections. ORG 9616 and ORG 9991 had shorter durations of action than ORG 9426. The duration of action of the doses that were five times the ED₉₀ was 18 ± 5.88 and 15.8 ± 4.41 min (mean ± sD) with ORG 9616 and ORG 9991, respectively, as compared with 39.7 ± 17.15 min with ORG 9426 (P < 0.05). ORG 9426 was virtually free of cardiovascular effects. The ED₉₀ doses of ORG 9616 and ORG 9991 did not cause cardiovascular effects; the doses of three and five times the ED₉₀ caused small decreases in mean arterial blood pressure and increases in heart rate. Mean arterial blood pressure decreased from 99 ± 10.2 to 88 ± 13.1 mm Hg and from 98 ± 11.7 to 77 ± 8.1 mm Hg with five times the ED₉₀ dose of ORG 9616 and ORG 9991, respectively. The authors conclude that ORG 9426 has a duration of neuromuscular blockade that is probably similar to vecuronium, and one that is free of cardiovascular effects. ORG 9616 and ORG 9991 have shorter durations of action, but cause decreases in arterial blood pressure and increases in heart rate with larger doses. The extent to which these cardiovascular changes may occur in humans will determine the ultimate clinical efficacy of these drugs.

Key Words: NEUROMUSCULAR RELAXANTS—ORG 9426, ORG 9616, ORG 9991.