PubMed · 10472254
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S M Tucker. 1999. Attention deficit hyperactivity disorder.. https://doi.org/10.1177/014107689909200501
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RATIONALE: Para-methoxyamphetamine (PMA) is a substituted amphetamine that has been responsible for a number of fatalities in Australia and North America. Previous investigators have shown that p-hydroxyamphetamine (PHA), the primary metabolite of PMA, has effects on central neurotransmitter kinetics in vitro that are similar to those of the parent compound. In order to understand the role of PHA, it is necessary to determine both the in vivo actions and the concentrations achieved relative to those of PMA. OBJECTIVES: The effects of PHA and PMA on 5-hydroxytryptamine (5HT) and dopamine kinetics in brain were determined and the concentrations of each compound measured in blood and brain. METHODS: Animals were housed at 20-22C on a standard 12/12-h light/dark cycle. High speed chronoamperometry was used to compare the ability of PMA and PHA to alter 5HT and dopamine kinetics in the rat striatum in vivo. Concentrations of PHA and PMA in blood, whole brain and striatum were determined following a dose of PMA (10 mg/kg, IP.) using HPLC with fluorescence detection. RESULTS: PHA was more effective than PMA at evoking neurotransmitter release and inhibiting the uptake of dopamine. However, both compounds were approximately equipotent 5HT uptake inhibitors. PMA and PHA concentrations in whole brain and striatum peaked within 30 min of the administered dose, whereas blood concentrations of both compounds peaked 1 h after the dose. PHA concentrations in both blood and brain were consistently much lower than PMA concentrations. CONCLUSIONS: These data indicate that although PHA is more effective than PMA at altering 5HT and dopamine kinetics in vivo, it is unlikely to achieve sufficient brain concentrations to contribute to the central effects of PMA.
The rapid increase in amphetamine abuse for recreational purposes has created a need for fast analysis and detection methodologies. For the first time, we show the separation of six amphetamines by ESI-IMS/MS. A complete analysis can be performed in 70 s, which is faster than traditional chromatographic techniques. In addition, ESI-IMS/MS was found to provide low detection limits for the six compounds (15.4 ppb for ethylamphetamine). Charge competition between amphetamines was found to occur at high amphetamine concentrations. The degree of preferential ionization was dependent on the functional group placed on the amine. Both one-analyte and two-analyte calibration curves were evaluated on the basis of the ion evaporation model. Evaporation rates were determined for the six amphetamines, and the rates were correlated with the degree of selective ionization. Evaluation of three typical ESI solvent compositions showed that the addition of a modifier (acetic acid and formic acid) enhanced the degree of preferential ionization for some amphetamines and increased the effect of charge competition. The solvent studies show the complexity of ESI and provide possible strategies for altering the amount of charge competition between analytes. Overall, ESI-IMS/MS appears to be a promising technique because of its sensitivity and rapid separation times for the amphetamines in aqueous samples; however, further research employing biological samples is required before it can be recommended as a mainstream technique.
AIM: This article provides the first comprehensive meta-analysis of randomized clinical trials of medications for obesity. METHOD: Based on stringent inclusionary criteria, a total of 108 studies were included in the final database. Outcomes are presented for comparisons of single and combination drugs to placebo and for comparisons of medications to one another. RESULT: Overall, the medications studied produced medium effect sizes. Four drugs produced large effect sizes (ie d>0.80; amphetamine, benzphetamine, fenfluramine and sibutramine). The placebo-subtracted weight losses for single drugs vs placebo included in the meta-analysis never exceeded 4.0 kg. No drug, or class of drugs, demonstrated clear superiority as an obesity medication. Effects of methodological factors are also presented along with suggestions for future research.