Myoneural effects of pethidine and droperidol

In vitro experiments on the rat phrenic nerve-hemidiaphragm preparation, stimulated directly or indirectly with supramaximal impulses at 0.1 Hz revealed that pethidine in concentrations greater than 5 micrograms ml-1 caused a rapid increase of the twitch. This was maximal (60% increase during direct and 70% increase during indirect stimulation) with pethidine 75 micrograms ml-1. With concentrations of pethidine greater than 40 micrograms ml-1, the initial increase was followed by a slowly developing inhibition of the twitch (50% depression with 46.0 and 50.4 micrograms ml-1 during direct and indirect stimulation, respectively). Droperidol caused no increase in twitch, but it depressed the twitch by 50% at concentrations of 9.8 and 6.9 micrograms ml-1 during direct and indirect stimulation, respectively. The increase in twitch produced by pethidine was augmented by 4-aminopyridine and inhibited by verapamil during both direct and indirect stimulation. Tubocurarine antagonized the augmentation of the twitch by pethidine only during indirect stimulation. The pethidine- and droperidol-induced inhibition of the twitch could be reversed by washout, but it was not antagonized by neostigmine or 4-aminopyridine. The inhibitory effect of pethidine and droperidol were additive. Sub-effective inhibitory concentrations of pethidine and droperidol, and those of tubocurarine, pancuronium and suxamethonium, independently of the sequence of their administration, mutually increased the myoneural effects of one another. The resulting twitch depression could be reversed by washout. The inhibition caused by the combination of pethidine with tubocurarine or pancuronium was partially antagonized by neostigmine or 4-aminopyridine.(ABSTRACT TRUNCATED AT 250 WORDS)