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Expert Opin Drug Saf. 2009 May;8(3):317-29. doi: 10.1517/14740330902931524.

Serotonergic drugs and valvular heart disease.

Author information

1
Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. rrothman@mail.nih.gov

Abstract

BACKGROUND:

The serotonin (5-HT) releasers (+/-)-fenfluramine and (+)-fenfluramine were withdrawn from clinical use owing to increased risk of valvular heart disease. One prevailing hypothesis (i.e., the '5-HT hypothesis') suggests that fenfluramine-induced increases in plasma 5-HT underlie the disease.

OBJECTIVE:

Here, we critically evaluate the possible mechanisms responsible for fenfluramine-associated valve disease.

METHODS:

Findings from in vitro and in vivo experiments performed in our laboratory are reviewed. The data are integrated with existing literature to address the validity of the 5-HT hypothesis and suggest alternative explanations.

CONCLUSIONS:

The overwhelming majority of evidence refutes the 5-HT hypothesis. A more likely cause of fenfluramine-induced valvulopathy is activation of 5-HT(2B) receptors on heart valves by the metabolite norfenfluramine. Future serotonergic medications should be designed to lack 5-HT(2B) agonist activity.

PMID:
19505264
PMCID:
PMC2695569
DOI:
10.1517/14740330902931524
[Indexed for MEDLINE]
Free PMC Article
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