A comparison of the kinetics of d- and l-amphetamine in the brain of isolated and aggregated rats

The kinetics of d- and l-amphetamine were investigated in isolated and aggregated male rats. The i.p. injection of 15 mg/kg of d- or l-¹⁴C-amphetamine was followed by the determination of drug concentrations in the cerebral cortex, hypothalamus, medulla oblongata-pons, cerebellum, striatum, hippocampus, and the whole brain after solvent extraction.In isolated rats, the disappearance curves of the labelled amphetamines were monoexponential. The half-lives of d- and l-amphetamine in whole brain were 1.2±0.1 and 1.3±0.1 h, respectively. In whole brains of aggregated rats the disappearance curves were biexponential (half-lives: d-amphetamine, 0.9±0.1 and 2.3±0.2 h; l-amphetamine, 0.7±0.1 and 2.3±0.1 h).For the brain areas of isolated rats, the elimination curves of amphetamines were monoexponential and the half-lives of d- and l-amphetamine were almost identical. In aggregated rats certain differences were observed. d-Amphetamine was eliminated from the striatum and hippocampus as a biexponential function, and l-amphetamine elimination was biphasic only in the striatum. In other brain regions both d- and l-amphetamine were eliminated as a monoexponential function. The half-lives of d-amphetamine in different brain areas were, however, shorter than those of the l-isomer.The observed differences between d- and l-amphetamine kinetics in brain areas of isolated and aggregated rats may explain certain aspects of the pharmacological activities of these drugs.