Effect of four amphetamines on brain biogenic amines and their metabolites

Abstract

The effect of D-amphetamine, D-methylamphetamine, p-nitro and p-bromomethylamphetamine on the release and turnover (as assessed by synthesis blockade) of brain noradrenaline and 5-HT have been studied in the rat. All the amphetamines increased the turnover of brain 5-HT but their mechanism of action in reducing the level of this amine appeared to differ. Thus methylamphetamine and p-nitromethylamphetamine potentiated the effect of 4-methyl-α-ethyl-meta-tyramine in depleting brain 5-HT, whereas the other two amphetamines were without effect. Similarly both methyl and p-nitromethylamphetamine significantly decreased the turnover of brain noradrenaline whereas the other amphetamines were without effect. The effect of these drugs on the noradrenaline, dopamine, 5-HT, normetanephrine and 5-hydroxyindole acetic acid concentration in the cortex, middle brain and caudal brain regions were also studied. p-Bromomethylamphetamine appeared to be unique in that it only affected the normetanephrine and 5-hydroxyindole acetic acid content of the middle brain region. The other amphetamines affected the metabolism of the biogenic amines in at least two of the three brain regions studied. These findings are discussed with respect to the different behavioural effects produced in animals by these drugs.