The potential effects of
propofol emulsion (
Diprivan) on the neuromuscular transmission and muscular contraction were studied using in vitro and in vivo nerve-muscle preparations of rats. The contractions of the isolated rat diaphragm elicited by either indirect or direct electrical stimulation were inhibited by
propofol emulsion at threshold concentrations of 42 and 112 mumol l-1, respectively. Similarly, the gastrocnemius muscle contractions induced by either indirect or direct electrical stimulation in vivo were inhibited by
propofol emulsion administration as a bolus injection of 2.5 mg kg-1 intravenously, followed by
intravenous infusion of 150 micrograms kg-1 min-1 for 1 h into rats. The inhibitory effects of
propofol in both preparations were greater with indirect rather than direct stimulation.
Propofol emulsion was found to be capable of enhancing the
paralysis of the indirectly stimulated rat diaphragm in vitro and gastrocnemius muscle in vivo induced by either
pipecuronium or
succinylcholine. The combination of
propofol and
pipecuronium led to a synergistic inhibition of the neuromuscular transmission, while the combination of
propofol and
succinylcholine led to additive inhibition. Pretreatment with
propofol emulsion at these threshold concentrations markedly inhibited the stimulant effects of
aminophylline and
digoxin on the indirectly and directly induced diaphragmatic contractions. Also, the enhancement effects of
aminophylline on the indirectly and directly and of
digoxin on indirectly induced rat gastrocnemius muscle contractions were markedly inhibited by
propofol emulsion administration to rats. Pretreatment with
propofol emulsion at the threshold concentrations enhanced the inhibitory effects of
verapamil on diaphragmatic contractions elicited either indirectly or directly and enhanced the inhibitory effect of
adenosine on the contractions elicited indirectly. Similarly, the inhibitory effects of
verapamil on the indirectly and directly and of
adenosine on indirectly induced rat gastrocnemius muscle contractions were markedly potentiated by
propofol emulsion administration to rats. In addition, doubling the concentration of
calcium in the bathing fluid produced no change in the inhibitory effects of
propofol emulsion on either indirectly or directly elicited diaphragmatic contractions, while doubling the concentration of external
magnesium potentiated the
propofol effects. Pretreatment with
4-aminopyridine suppressed the inhibitory effects of
propofol emulsion on diaphragmatic contractions elicited either indirectly or directly. These results suggest that
propofol acts presynaptically to inhibit the neuromuscular transmission and acts at the muscle membrane to inhibit the muscular contraction.