Some neurochemical effects of amphetamine, methylamphetamine and p-bromomethylamphetamine in the rat.

1. Low doses of D-amphetamine increased brain noradrenaline concentrations in the rat; doses greater than 5 mg/kg, however, caused a decrease. Methylamphetamine also showed this dual effect, but a reduction in brain noradrenaline concentration only occurred when doses greater than 10 mg/kg were administered. p-Bromomethylamphetamine did not significantly reduce brain noradrenaline concentrations even at a dose of 60 mg/kg. The order of potency in reducing the concentration of noradrenaline correlated with the central stimulant effects; D-amphetamine produced the greatest and p-bromomethylamphetamine the least increase in motor activity.2. D-Amphetamine and D-methylamphetamine potentiated the action of 4,alpha-dimethyl-m-tyramine (H77/77) in depleting brain noradrenaline; the greatest potentiation was produced by D-amphetamine. This suggests that the phenylethylamines may affect brain noradrenaline concentrations by acting on the reserpine resistant uptake mechanism.3. Differences were found in the effect of the three drugs on brain dopamine concentrations; D-amphetamine caused a decrease while p-bromomethylamphetamine caused an increase. Methylamphetamine had no effect on the concentration of dopamine. Only p-bromomethylamphetamine significantly reduced the depletion of brain dopamine concentrations caused by H77/77.4. Methylamphetamine and p-bromomethylamphetamine reduced the concentration of 5-hydroxytryptamine (5-HT) in the brain; administration of the same dose of D-amphetamine did not change the concentration of 5-HT.5. Changes in the blood and brain concentrations of tyrosine and tryptophan, and in the concentration of gamma-amino-n-butyric acid in the brain could not be correlated with the changes observed in the concentrations of biogenic amines in the brain.