QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.106.101618v1 318/2/604    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zolkowska, D. Articles by Baumann, M. H. Search for Related Content PubMed PubMed Citation Articles by Zolkowska, D. Articles by Baumann, M. H.

CARDIOVASCULAR

Amphetamine Analogs Increase Plasma Serotonin: Implications for Cardiac and Pulmonary Disease

Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland

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 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.

Address correspondence to: Dr. Michael H. Baumann, Clinical Psychopharmacology Section, IRP, NIDA, National Institutes of Health, Department of Health and Human Services, 5500 Nathan Shock Drive, Baltimore, MD 21224. E-mail: mbaumann{at}intra.nida.nih.gov

This article has been cited by other articles:

				R. A. Pena-Silva, J. D. Miller, Y. Chu, and D. D. Heistad Serotonin produces monoamine oxidase-dependent oxidative stress in human heart valves Am J Physiol Heart Circ Physiol, October 1, 2009; 297(4): H1354 - H1360. [Abstract] [Full Text] [PDF]

				S. R. Raj, C. M. Stein, P. J. Saavedra, and D. M. Roden Cardiovascular Effects of Noncardiovascular Drugs Circulation, September 22, 2009; 120(12): 1123 - 1132. [Full Text] [PDF]

				S. Droogmans, D. Kerkhove, B. Cosyns, and G. Van Camp Role of echocardiography in toxic heart valvulopathy Eur J Echocardiogr, June 1, 2009; 10(4): 467 - 476. [Abstract] [Full Text] [PDF]

				C. Fligny, Y. Fromes, P. Bonnin, M. Darmon, E. Bayard, J.-M. Launay, F. Cote, J. Mallet, and G. Vodjdani Maternal serotonin influences cardiac function in adult offspring FASEB J, July 1, 2008; 22(7): 2340 - 2349. [Abstract] [Full Text] [PDF]

				E. K. Weir, M. Obreztchikova, and Z. Hong Fenfluramine: riddle or Rosetta stone? Eur. Respir. J., February 1, 2008; 31(2): 232 - 235. [Full Text] [PDF]

				D. Zolkowska, M. H. Baumann, and R. B. Rothman Chronic Fenfluramine Administration Increases Plasma Serotonin (5-Hydroxytryptamine) to Nontoxic Levels J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 791 - 797. [Abstract] [Full Text] [PDF]

				R. B. Rothman and M. H. Baumann Methamphetamine and Idiopathic Pulmonary Arterial Hypertension: Role of the Serotonin Transporter Chest, October 1, 2007; 132(4): 1412 - 1413. [Full Text] [PDF]

				A. Papageorgiou and C. Denef Stimulation of Growth Hormone Release by 5-Hydroxytryptamine (5-HT) in Cultured Rat Anterior Pituitary Cell Aggregates: Evidence for Mediation by 5-HT2B, 5-HT7, 5-HT1B, and Ketanserin-Sensitive Receptors Endocrinology, September 1, 2007; 148(9): 4509 - 4522. [Abstract] [Full Text] [PDF]

				A. Papageorgiou and C. Denef Estradiol Induces Expression of 5-Hydroxytryptamine (5-HT) 4, 5-HT5, and 5-HT6 Receptor Messenger Ribonucleic Acid in Rat Anterior Pituitary Cell Aggregates and Allows Prolactin Release via the 5-HT4 Receptor Endocrinology, March 1, 2007; 148(3): 1384 - 1395. [Abstract] [Full Text] [PDF]

				E. D. Willers and J. H. Newman New Risks for Pulmonary Hypertension: Need for a Large Epidemiologic Study Chest, December 1, 2006; 130(6): 1633 - 1635. [Full Text] [PDF]