EFFECT OF ATRACURIUM AND LAUDANOSINE ON THE RELEASE OF 3H-NORADRENALINE

We examined the effects of atracurium and its breakdown product,laudanosine, on resting and stimulation-evoked release of ³H-noradrenaline(³H-NA) from sympathetic axon terminals of isolated right atriaof guineapigs. Both atra-curium 1–100 µmol litre^–1and laudanosine 1–50 µmol litre^–1 enhancedthe release of ³H-NA evoked by field stimulation (2 Hz, 24 stimuli),but did not affect resting release. When the production of laudanosinefrom atracurium was inhibited by maintaining the atracuriumsolution at 4 °C, atracurium did not enhance the releaseof ³H-NA as occured when it was kept at 37 °C. However,atracurium antagonized the inhibitory effect of oxotremorineon release of ³H-NA, whereas laudanosine did not. These datasuggest that atracurium possesses and antimuscarinic effect.Its metabolite, laudanosine, in concentrations which would beexpected following prolonged administration of atracurium, produceda marked increase in release of ³H-NA. This effect of laudanosinemay explain some of the unwanted effects seen following administrationof atracurium.