Brien J F, Kitney J C, Peachey J E, Rogers B J
Res Commun Chem Pathol Pharmacol. 1978 Nov;22(2):313-28.
(+)-Methamphetamine (MA) produced dose-related behavioural changes in mice. There was a correlation between the type of behavioural response and the peak brain MA concentration after the i.p. administration of each of the following doses of (+)-MA: 0.64 mg/kg (decreased quiescence--0.738 microgram/g MA), 2.5 mg/kg (increased locomotor activity--3.148 microgram/g MA) and 10.0 mg/kg (stereotyped behaviour--12.608 microgram/g MA). During the 90-min experimental period, there was no positive correlation between the magnitude of each type of drug-induced behaviour and the brain MA concentration. For 10.0 mg/kg (+)-MA, there was a negative correlation between the drug-induced stereotyped behaviour and the brain MA concentration. The apparent disappearance half-life of MA from brain was dependent on the dose of (+)-MA: 0.64 mg/kg (t1/2 56.6 min), 2.5 mg/kg (t1/2 66.6 min), 10.0 mg/kg (42.2 min). For the three (+)-MA doses, the metabolite amphetamine (A) also was present in the brain and the A/MA + A brain concentration ratio was 0.11--0.14. This metabolite appeared to have only a small involvement in the MA-induced behavioural effects.
（+）-甲基苯丙胺（MA）可使小鼠产生与剂量相关的行为变化。腹腔注射下列不同剂量的（+）-MA后，行为反应类型与脑内MA浓度峰值之间存在相关性：0.64 mg/kg（静息减少——0.738微克/克MA）、2.5 mg/kg（运动活性增加——3.148微克/克MA）和10.0 mg/kg（刻板行为——12.608微克/克MA）。在90分钟的实验期内，每种药物诱导行为的幅度与脑内MA浓度之间无正相关。对于10.0 mg/kg的（+）-MA，药物诱导的刻板行为与脑内MA浓度之间存在负相关。MA在脑内的表观消除半衰期取决于（+）-MA的剂量：0.64 mg/kg（t1/2 56.6分钟）、2.5 mg/kg（t1/2 66.6分钟）、10.0 mg/kg（42.2分钟）。对于三种（+）-MA剂量，代谢产物苯丙胺（A）也存在于脑内，且脑内A/MA+A浓度比为0.11——0.14。该代谢产物似乎对MA诱导的行为效应影响较小。
