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

The Journal of Pharmacology and Experimental Therapeutics
Dorota ZolkowskaMichael H Baumann

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, increase...Continue Reading

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Citations

Dec 18, 2008·Experimental and Clinical Psychopharmacology·Richard B RothmanMichael H Baumann
Jun 29, 2010·Journal of Child and Adolescent Psychopharmacology·Mehmet Goksin KaramanAyten Erdogan
Apr 9, 2009·American Journal of Therapeutics·Richard B Rothman
Aug 12, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Ricardo A Peña-SilvaDonald D Heistad
Sep 23, 2009·Circulation·Satish R RajDan M Roden
Jun 23, 2009·American Journal of Respiratory Cell and Molecular Biology·Sandra M WellsAndrij Holian
Jun 14, 2013·Clinical Reviews in Allergy & Immunology·Will TsengTimothy E Albertson
Jun 10, 2009·Expert Opinion on Drug Safety·Richard B Rothman, Michael H Baumann
Sep 21, 2010·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Leo J SchepD Michael G Beasley
Jul 4, 2012·Neuroscience·P KoesterJ Daumann
Dec 15, 2006·Chest·Elisabeth D Willers, John H Newman
Mar 9, 2010·International Journal of Cardiology·Richard B Rothman, Ed J Hendricks
Nov 11, 2008·Annals of the New York Academy of Sciences·Richard B RothmanMichael H Baumann
Nov 11, 2008·Annals of the New York Academy of Sciences·Riccardo RuffoliFrancesco Fornai
May 20, 2014·Pharmacology & Therapeutics·Rae R MatsumotoJames P O'Callaghan
Apr 16, 2014·Biomedical Chromatography : BMC·Samanta Yubero-LahozRafael de la Torre
Nov 15, 2011·European Journal of Pharmacology·Samanta Yubero-LahozMichael H Baumann
Jan 25, 2014·Neuropharmacology·Leslie IversenRic Treble
Sep 6, 2008·Progress in Brain Research·Richard B RothmanMichael H Baumann
Mar 28, 2009·European Journal of Echocardiography : the Journal of the Working Group on Echocardiography of the European Society of Cardiology·Steven DroogmansGuy Van Camp
Oct 12, 2012·Journal of Psychopharmacology·Cheryl M CollinsJ Martin Elliott
Sep 12, 2018·Annals of Plastic Surgery·Soobin LimFrank H Lau
Jul 26, 2011·Yonsei Medical Journal·Ed J Hendricks, Richard B Rothman
May 12, 2019·International Journal of Molecular Sciences·James FrancescangeliAnthony Bonavia
Nov 23, 2007·The Journal of Pharmacology and Experimental Therapeutics·Dorota ZolkowskaRichard B Rothman
Feb 13, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Cécile FlignyGuilan Vodjdani
Mar 2, 2019·Medical Sciences : Open Access Journal·Daniela García-AlonsoJorge Skiold López-Canales
Jan 1, 2018·Advances in Pulmonary Hypertension·Ramon L RamirezRoham T Zamanian

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