Interactions between ORG9426 and other non-depolarizing neuromuscular blocking agents in ratsin vivo

Abstract

In this study, combined neuromuscular blocking effects of ORG9426 with other non-depolarizing neuromuscular blocking agents were investigated. About 20% steady state neuromuscular block was established by a continuous infusion of one of 6 neuromuscular blocking agents (ORG9426, vecuronium, pancuronium, pipecuronium, d-tubocurarine and metocurine). Then 1/7 of the ED50 of ORG9426 or one of other neuromuscular blocking agents was administered in a single injection, and the increase in the neuromuscular block was observed. The combined neuromuscular blocking effect of ORG9426 and d-tubocurarine or ORG9426 and metocurine was significantly ( P < 0.05) greater than that of each corresponding control (the combination of same neuromuscular blocking agent). The effect of d-tubocurarine was also potentiated by vecuronium, pancuronium and pipecuronium. These potentiations were not observed between ORG9426 and pancuronium, pipecuronium or vecuronium. Possible mechanisms of these synergistic interactions were discussed.

Pharmacoeconomics and Pharmacodynamic Interactions of Rocuronium and Pancuronium

“…ere are no earlier studies using this combination in conditions simulating clinical intubation. Golpariaini and colleagues, on phrenic-nervehemi-diaphragm preparations of male Sprague-Dawley rats, constructed isobolograms from the IC50 values and shown that ORG9426 potentiates pancuronium [25,26]. However, Naguib by the isobolographic analysis observed additive interaction between rocuronium and pancuronium [27].…”