Myorelaxant effect of diazepam. Interactions with neuromuscular blocking agents and cholinergic drugs

Experiments were performed, using electrophysiological techniques, to investigate the effects and interactions of diazepam with commonly-used neuromuscular blocking agents and cholinergic agonists in chick and rat isolated nerve-muscle preparations. The results showed that in low concentrations (3.4-340 mumol/l, i.e. 1-100 micrograms ml-1) diazepam increased, in a dose-dependent manner, the twitch contractions in response to motor nerve stimulation of the chick and rat. High concentrations of diazepam (greater than 340 mumol/l) decreased the twitch tension and greatly reduced the contractures produced by acetylcholine (ACh) and tetraethylammonium (TEA) in the chick skeletal muscle. However, in the concentration range studied (close to a therapeutic dose of 0.15 mg kg-1), diazepam had no significant effect on the neuromuscular blockade produced either by tubocurarine or by succinylcholine. It was concluded that diazepam may either increase or decrease the twitch tension, in rat and chick skeletal muscle, the effect being dependent on the concentrations used. The mechanism of action of diazepam may depend on an increasing intracellular calcium concentration, which is directly involved in the increase of the twitch tension by low concentrations of diazepam.