Neuromuscular blockade induced by flunarizine alone and in combination with pancuronium, suxamethonium or neomycin: studies in isolated rat phrenic-hemidiaphragm preparations.

The in vitro effects of flunarizine on indirectly- and directly-elicited contractions in rat phrenic-hemidiaphragm preparations were studied. The interactions of flunarizine with non-depolarizing and depolarizing neuromuscular blocking drugs (pancuronium and suxamethonium) and with an aminoglycoside antibiotic (neomycin) were also evaluated. Flunarizine induced a slowly developing concentration-dependent reduction of indirectly-elicited diaphragm twitch height, but only slightly reduced directly-elicited contractions. Flunarizine 1 and 5 mumol.l-1 produced a concentration-dependent enhancement of pancuronium-induced neuromuscular blockade, whereas suxamethonium blockade was significantly increased by flunarizine 5 mumols.l.-1 only. Moreover, both flunarizine 1 and 5 mumols.l-1 also increased the neuromuscular blockade induced by neomycin. In conclusion, flunarizine induced neuromuscular blockade and enhanced the effects of several neuromuscular blocking agents to varying degrees in vitro.