Amphetamine analogs increase plasma serotonin: implications for cardiac and pulmonary disease.

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Zolkowska D, Rothman RB, Baumann MH

Amphetamine analogs increase plasma serotonin: implications for cardiac and pulmonary disease.

J Pharmacol Exp Ther. 2006 Aug;318(2):604-10. Epub 2006 Apr 27.

PubMed ID

16644904 [ View in PubMed

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Abstract

Elevations in plasma serotonin (5-HT) have been implicated in the pathogenesis of cardiac and pulmonary disease. Normally, plasma 5-HT concentrations are kept low by transporter-mediated uptake of 5-HT into platelets and by metabolism to 5-hydroxyindoleacetic acid (5-HIAA). Many abused drugs (e.g., substituted amphetamines) and prescribed medications (e.g., fluoxetine) target 5-HT transporters and could thereby influence circulating 5-HT. We evaluated the effects of amphetamines analogs [(+/-)-fenfluramine, (+/-)-3,4-methylenedioxymethamphetamine, (+)-methamphetamine, (+)-amphetamine, phentermine] on extracellular levels (i.e., plasma levels) of 5-HT and 5-HIAA in blood from catheterized rats. Effects of the 5-HT uptake blocker fluoxetine were examined for comparison. Drugs were tested in vivo and in vitro; plasma indoles were measured using a novel microdialysis method in whole blood. We found that baseline dialysate levels of 5-HT are approximately 0.22 nM, and amphetamine analogs evoke large dose-dependent increases in plasma 5-HT ranging from 4 to 20 nM. The ability of drugs to elevate plasma 5-HT is positively correlated with their potency as 5-HT transporter substrates. Fluoxetine produced small, but significant, increases in plasma 5-HT. Although the drug-evoked 5-HT concentrations are below the micromolar levels required for contraction of pulmonary arteries, they approach concentrations reported to stimulate mitogenesis in pulmonary artery smooth muscle cells. Additional studies are needed to determine the effects of chronic administration of amphetamines on circulating 5-HT.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Phentermine	Sodium-dependent serotonin transporter	Protein	Humans	Yes	Inhibitor	Details