Kinetics and metabolism of amphetamine in the brain of rats of different ages

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Abstract
The kinetics and tissue distribution of amphetamine and its metabolites p-hydroxyamphetamine (p-OH-A) and p-hydroxynorephedrine (p-OH-NE) were investigated in young adult (3–4 months) and old (20–25 months) male rats, after i.p. injection of 5 mg/kg tritium labelled d-amphetamine. The concentrations of these drugs were determined in plasma, cerebral cortex, brainstem and hypothalamus, by thin layer chromatography. 1. From 60 min up to 4 hrs after injection of amphetamine the concentration of a mphetamine in plasma and brain tissue of old rats was significantly (P brain stem > hypothalamus. 2. The blood-brain barrier is permutle to p-OH-A; 10 to 20 min after i.v. injection of 10 μCi/kg of p-OH-A (10 mCi/m mole) the ratio brain/blood plasma was found to be 1:3. The half life of p-OH-A in blood plasma was almost identical after injection of amphetamine and p-OH-A (90 min and 98 min respectively). 3. The levels of p-OH-NE in different brain areas were significantly lower (P<0.05) in old animals than in young adult rats 4 hrs after application of amphetamine. This metabolite of amphetamine shows a higher concentration in the hypothalamus earlier than in other brain regions.