Clinical pharmacology of ORG 7617, a short-acting non-depolarizing neuromuscular blocking agent.
The dose-response relationship and the time course of action of Org 7617, a short acting non-depolarizing neuromuscular blocking agent, were evaluated during thiopentone, fentanyl, halothane and N2O anaesthesia. Neuromuscular transmission was monitored mechanomyographically. The ED50 and ED90 were calculated after single bolus doses of the drug. Twelve, seven and three patients received 2.5, 3.75 or 5.0 mg.kg-1 Org 7617, respectively. Neuromuscular block was characterized by a short lag time (average 30 s) and rapid development of neuromuscular block (69-84 s). Maximum block approximated to 66%, 91% and 95%, and the duration until clinically adequate recovery (TOF ratio of 0.7) to 7.4, 12.1 and 12.2 min after 2.5, 3.75, 5 mg.kg-1 of Org 7617, respectively. The calculated ED50 and ED90 were 1.8 and 3.4 mg.kg-1. Adverse effects, including a moderate fall in systolic and diastolic arterial blood pressure and a concomitant increase in heart rate appeared to be dose-dependent. Some patients showed flushing. One patient given 5 mg/kg Org 7617 had serious adverse effects suggestive of histamine release, i.e. flushing, urticaria, tachycardia, hypotension and bronchospasm. Therefore further clinical investigations were terminated. Although its low potency and the adverse effects observed will prevent further clinical development of ORG 7617, the results do support the contention that it is feasible to develop short-acting non-depolarizing neuromuscular blocking agents from the steroidal series.
van den Broek
L
L
Department of Anesthesiology, University Hospital of Groningen, The Netherlands.
Wierda
J M
JM
Proost
J H
JH
Hommes
F D
FD
Agoston
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000758:Anesthesia; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009469:Neuromuscular Junction / Q000187:drug effects; D003473:Neuromuscular Nondepolarizing Agents / Q000009:adverse effects / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors; D014673:Vecuronium Bromide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology
D003473:Neuromuscular Nondepolarizing Agents; C058720:Org 7617; D014673:Vecuronium Bromide