Cardiovascular and neuromuscular effects of three steroidal neuromuscular blocking drugs in dogs (ORG 9616, ORG 9426, ORG 9991).
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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Cason
B
B
Department of Anesthesia, University of California, San Francisco 94143-0648.
Baker
D G
DG
Hickey
R F
RF
Miller
R D
RD
Agoston
S
S
D000732:Androstanols / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D006439:Hemodynamics / Q000187:drug effects*; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects*; D000077123:Rocuronium; D013329:Structure-Activity Relationship; D014673:Vecuronium Bromide / Q000031:analogs & derivatives* / Q000494:pharmacology
D000732:Androstanols; D009466:Neuromuscular Blocking Agents; C058721:Org 9616; C063470:ORG 9991; D014673:Vecuronium Bromide; D000077123:Rocuronium