Distribution of amphetamine and its hydroxylated metabolites in various areas of the rat brain
Jori, A.; Caccia, S.
Journal of Pharmacy and Pharmacology 26(9): 746-748
1974
ISSN/ISBN: 0022-3573 PMID: 4155759 Document Number: 81284
Rats were injected i.p. with (+)-amphetamine sulfate at 15, 10 or 5 mg/kg and were decapitated 1, 2, 5, 8 and 12 h after the dose. The cerebellum, brainstem, striatum and the remaining hemispheres were dissected and determinations were made on single or pooled areas. Amphetamine reached high levels in all the areas studied, but it seemed preferentially localized in the brainstem and hemispheres. At 12 h after administration the levels of the drug were less than 1/100th of those found in the same area 1 h after the injection. p-Hydroxyamphetamine showed a distribution similar to that of amphetamine, although at a different range of concentrations. p-Hydroxynorephedrine reached maximum levels at 5 h after the dose of amphetamine and accumulated in decreasing order in brainstem, hemispheres, cerebellum and striatum. The persistence of large concentrations of p-hydroxynorephedrine in a noradrenergic area, such as the brainstem, is consistent with the hypothesis that this metabolite is retained in the noradrenaline nerve endings and is responsible for the amphetamine-induced long-lasting noradrenaline depletion.