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)

Naloxone fails to antagonize halothane-induced depression of the longitudinal muscle of the guinea pig ileum.

The influence of halothane, or naloxone, or halothane followed by naloxone was investigated in the in vitro myenteric plexus longitudinal muscle preparation of the guinea pig ileum. Halothane alone in 1.5 to 2.0% (v/v) concentration caused about 50% depression of the twitch and decreased both spontaneous acetylcholine (ACh) release (p less than 0.02) and volley output of ACh (p less than 0.02). Very high concentrations (greater than 1 micron) of naloxone caused a nonspecific, postsynaptic depression of the twitch. Higher than 100 nM concentrations of naloxone increased spontaneous ACh release, but had no effect on the volley output of ACh. Over a wide concentration range, from 15 nM to 3 micron, naloxone did not antagonize in the longitudinal muscle preparation the effects of halothane on any of the parameters investigated. These findings indicate that the sites of action of halothane and naloxone in this preparation are not identical.

Naloxone fails to antagonize thiopental anesthesia.

A study was undertaken to determine the effect in man of naloxone on the central nervous system depression produced by IV thiopental. Eight normal volunteers were given 5 mg/kg thiopental IV. On a separate occasion the same 8 volunteers were given 50 microgram/kg naloxone IV 5 minutes prior to 5 mg/kg thiopental. Naloxone had no significant effect on the rate of return of consciousness following administration of thiopental. Naloxone also had no significant effect on the responses of blood pressure, heart rate, or respiratory rate to thiopental.