A combined study of pharmacodynamics and pharmacokinetics of methamphetamine and its metabolite in male mice

Abstract Background Methamphetamine (METH) is typically characterized as a potent dependent psychostimulant. Various behavioral models have been used to study METH drug dependence. The objective of this study was to determine the time period during which the neuropharmacological effects of METH are most pronounced, through a combined study of pharmacodynamics and pharmacokinetics. Methods The present study simultaneously investigated the pharmacodynamics and pharmacokinetics of METH and its metabolite amphetamine (AMP) in mice by measuring the locomotor activity level and the concentrations of METH and AMP in the blood and brain from 5 min to 8 h after administration. Results The pharmacodynamic analysis showed that the mice maintained a high level of activity from 5 min to 1 h after the administration, followed by a significant decrease in activity at 2 h. The pharmacokinetic analysis showed that METH was rapidly absorbed into the blood, and its concentration reached the peak value at 5 min. AMP concentration in blood increased and reached the peak value at 1 h; the concentrations of METH and AMP in the brain both reached the peak value at 30 min. Conclusions In terms of pharmacodynamics and pharmacokinetics, the behavioral effects of METH on mice are most obvious within 1 h, at most 2 h, after administration, which can thus be considered a preferred time period to study the neuropharmacology effects of METH.