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• W2080471968 abstract "Phendimetrazine is an effective and widely prescribed appetite suppressant. Preclinical findings show that phendimetrazine displays stimulant properties similar to amphetamine, but few studies have examined the neurochemical mechanism of the drug. In the present work, we characterize the activity of phendimetrazine and its putative metabolites [phenmetrazine, pseudophenmetrazine, and associated stereoisomers] at biogenic amine transporters. All drugs were tested in vitro using assays to measure uptake and release of [3H]dopamine, [3H]norepinephrine, and [3H]serotonin ([3H]5-HT) in rat brain synaptosomes. Selected drugs were tested in vivo using microdialysis to measure extracellular dopamine and serotonin (5-HT) in rat nucleus accumbens. Phendimetrazine itself had no effect on uptake or release of any transmitter. In contrast, the trans-configured N-demethylated metabolite, phenmetrazine, was a potent releaser of [3H]norepinephrine (EC(50)=50 nM) and [3H]dopamine (EC(50)=131 nM). The cis N-demethylated metabolite, pseudophenmetrazine, displayed modest potency at releasing [3H]norepinephrine (EC(50)=514 nM) and blocking [3H]dopamine re-uptake (IC(50)=2630 nM). All drugs tested were inactive or weak in the [3H]5-HT assays. When injected intravenously, phendimetrazine had minimal effects on extracellular transmitter levels, whereas phenmetrazine produced dose-related elevations in extracellular dopamine. The collective findings suggest that phendimetrazine is a prodrug that is converted to the active metabolite phenmetrazine, a potent substrate for norepinephrine and dopamine transporters." @default.
• W2080471968 created "2016-06-24" @default.
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• W2080471968 date "2002-06-01" @default.
• W2080471968 modified "2023-09-23" @default.
• W2080471968 title "Interaction of the anorectic medication, phendimetrazine, and its metabolites with monoamine transporters in rat brain" @default.
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• W2080471968 doi "https://doi.org/10.1016/s0014-2999(02)01830-7" @default.
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