Presynaptic effect of I.V. anaesthetic agents at the neuromuscular junction

The effect of Althesin, diazepam, ketamine, propanidid and thiopentone on the release of acetylcholine was tested at the mouse neuromuscular junction. Althesin, diazepam and thiopentone increased the quantal content of the end-plate potential. Ketamine at low concentration (3.6 micromol litre-1) had a similar effect, but at high concentration (116.7 micromol litre-1) quantal content decreased sharply. Propanidid and cremophor EL did not affect quantal content. The increase in quantal content antagonized the effect of postsynaptic depression on the amplitude of the end-plate potential. The lack of enhancement of acetylcholine release appears to explain the in vitro interaction of propanidid with tubocurarine. The diversity of presynaptic actions of these drugs makes it unlikely that this is an important mechanism in producing anaesthesia.