Effect of amezinium on the release and catabolism of 3H-monoamines in brain slices

Abstract

Occipitocortical slices of rats were preincubated with [ 3H]noradrenaline or [ 3H]serotonin; striatal slices were preincubated with [ 3H]dopamine. The outflow of 3H-compounds was studied. In slices preincubated with [ 3H]noradrenaline, 1 nM amezinium diminished the outflow of deaminated metabolites (mainly [ 3H]-3,4-dihydroxyphenylglycol). Higher concentrations in addition released [ 3H]noradrenaline. The effects were antagonized by cocaine. In slices preincubated with [ 3H]dopamine, 1 nM amezinium caused no change, but 10 nM amezinium decreased the outflow of deaminated products (mainly [ 3H]-3,4-dihydroxyphenylacetic acid). Higher concentrations in addition released [ 3H]dopamine. The effects were antagonized by nomifensine. In experiments with [ 3H]serotonin, 1 nM amezinium caused no change, but 10 nM amezinium reduced the outflow of [ 3H]-5-hydroxyindoleacetic acid. Higher concentrations in addition released [ 3H]serotonin. The effects were antagonized by paroxetine. When amezinium was injected in vivo 1 hr before sacrifice, up to 10 mg/kg did not change the deamination of [ 3H]noradrenaline in cortical cubes; amezinium (50 mg/kg) caused slight inhibition. The results indicate that amezinium, added in vitro, is a very potent inhibitor of the MAO inside cerebral noradrenergic neurones. It is less potent at dopaminergic and serotonergic neurones. When injected systemically in vivo, however, amezinium at moderate doses has no effect on central monoamine catabolism, probably because of exclusion from the brain by the blood-brain barrier.