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 atria of guinea pigs. Both atracurium 1-100 mumol litre-1 and laudanosine 1-50 mumol litre-1 enhanced the release of 3H-NA evoked by field stimulation (2 Hz, 24 stimuli), but did not affect resting release. When the production of laudanosine from atracurium was inhibited by maintaining the atracurium solution at 4 degrees C, atracurium did not enhance the release of 3H-NA as occurred when it was kept at 37 degrees C. However, atracurium antagonized the inhibitory effect of oxotremorine on release of 3H-NA, whereas laudanosine did not. These data suggest that atracurium possesses an antimuscarinic effect. Its metabolite, laudanosine, in concentrations which would be expected following prolonged administration of atracurium, produced a marked increase in release of 3H-NA. This effect of laudanosine may explain some of the unwanted effects seen following administration of atracurium.