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|dc.identifier.citation||Psychopharmacology, 2002; 160(2):155-160||en|
|dc.description||The original publication is available at www.springerlink.com||en|
|dc.description.abstract||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 20–22°C 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.||en|
|dc.description.statementofresponsibility||Lisa M. Kaminskas; Rodney J. Irvine; Paul D. Callaghan; Jason M. White; Paul Kirkbride||en|
|dc.subject||p-methoxyamphetamine; p-hydroxyamphetamine; metabolism of p-methoxyamphetamine; neurotransmitter kinetics; core body temperature; heart rate||en|
|dc.title||The contribution of the metabolite p-hydroxyamphetamine to the central actions of p-methoxyamphetamine||en|
|Appears in Collections:||Pharmacology publications|
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