The effects of amiodarone, an α and β receptor antagonist, on adrenergic transmission in the cat spleen

The anti-anginal drug amiodarone produced a dose dependent reduction in the overflow of transmitter from the isolated blood perfused cat spleen following nerve stimulation at 30 Hz. In the presence of phenoxybenzamine (30 μg/ml) the normal increase in overflow of transmitter, following 200 stimuli at 10 Hz was prevented. This effect occurred whatever the order of addition of phenoxybenzamine and amiodarone, indicating that amiodarone did not reduce the overflow by stimulation of inhibitory presynaptic α receptors. In experiments in which the transmitter stores were labelled with [³H](-)-noradrenaline, amiodarone inhibited the release of label following nerve stimulation but had no effect on release induced by tyramine. Responses of the spleen to both nerve stimulation and tyramine were reduced by amiodarone but uptake of [³H](-)-noradrenaline given as injections (pulses) or as infusions, was not significantly affected. The effects of amiodarone on nerve evoked overflow of transmitter are not therefore related to changes in uptake of noradrenaline or to selective stimulation of presynaptic α receptors but probably reflect a neurone blocking action of the drug.