PMID- 22356640
OWN - NLM
STAT- MEDLINE
DCOM- 20120531
LR  - 20231104
IS  - 1365-2036 (Electronic)
IS  - 0269-2813 (Print)
IS  - 0269-2813 (Linking)
VI  - 35
IP  - 7
DP  - 2012 Apr
TI  - Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed 
      for gastrointestinal disorders.
PG  - 745-67
LID - 10.1111/j.1365-2036.2012.05011.x [doi]
AB  - BACKGROUND: The nonselective 5-HT(4) receptor agonists, cisapride and tegaserod 
      have been associated with cardiovascular adverse events (AEs). AIM: To perform a 
      systematic review of the safety profile, particularly cardiovascular, of 5-HT(4) 
      agonists developed for gastrointestinal disorders, and a nonsystematic summary of 
      their pharmacology and clinical efficacy. METHODS: Articles reporting data on 
      cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 
      (velusetrag) and ATI-7505 (naronapride) were identified through a systematic 
      search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 
      2006-2008 and DDW 2008-2010 were searched for these drug names, and 
      pharmaceutical companies approached to provide unpublished data. RESULTS: 
      Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data 
      with these 5-HT(4) agonists, are reviewed and summarised nonsystematically. 
      Articles relating to cardiac safety and tolerability of these agents, including 
      any relevant case reports, are reported systematically. Two nonselective 5-HT(4) 
      agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and 
      tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac 
      potassium channel and 5-HT(1) receptor subtypes have been suggested to account 
      for these effects. No cardiovascular safety concerns were reported for the newer, 
      selective 5-HT(4) agonists prucalopride, velusetrag, naronapride, or for 
      nonselective 5-HT(4) agonists with no hERG or 5-HT(1) affinity (renzapride, 
      clebopride, mosapride). CONCLUSIONS: 5-HT(4) agonists for GI disorders differ in 
      chemical structure and selectivity for 5-HT(4) receptors. Selectivity for 5-HT(4) 
      over non-5-HT(4) receptors may influence the agent's safety and overall 
      risk-benefit profile. Based on available evidence, highly selective 5-HT(4) 
      agonists may offer improved safety to treat patients with impaired GI motility.
CI  - (c) 2012 Blackwell Publishing Ltd.
FAU - Tack, J
AU  - Tack J
AD  - Department of Clinical and Experimental Medicine, University of Leuven, Belgium. 
      jan.tack@med.kuleuven.be
FAU - Camilleri, M
AU  - Camilleri M
FAU - Chang, L
AU  - Chang L
FAU - Chey, W D
AU  - Chey WD
FAU - Galligan, J J
AU  - Galligan JJ
FAU - Lacy, B E
AU  - Lacy BE
FAU - Muller-Lissner, S
AU  - Muller-Lissner S
FAU - Quigley, E M M
AU  - Quigley EM
FAU - Schuurkes, J
AU  - Schuurkes J
FAU - De Maeyer, J H
AU  - De Maeyer JH
FAU - Stanghellini, V
AU  - Stanghellini V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PT  - Systematic Review
DEP - 20120222
PL  - England
TA  - Aliment Pharmacol Ther
JT  - Alimentary pharmacology & therapeutics
JID - 8707234
RN  - 0 (Gastrointestinal Agents)
RN  - 0 (Indoles)
RN  - 0 (Serotonin 5-HT4 Receptor Agonists)
RN  - 458VC51857 (tegaserod)
RN  - UVL329170W (Cisapride)
SB  - IM
CIN - Aliment Pharmacol Ther. 2012 May;35(10):1243-4. PMID: 22500472
MH  - Cardiovascular Diseases/*chemically induced
MH  - Cisapride/adverse effects/pharmacology
MH  - Gastrointestinal Agents/*adverse effects/pharmacology
MH  - Gastrointestinal Diseases/*drug therapy
MH  - Humans
MH  - Indoles/adverse effects/pharmacology
MH  - Randomized Controlled Trials as Topic
MH  - Serotonin 5-HT4 Receptor Agonists/*adverse effects/pharmacology
PMC - PMC3491670
EDAT- 2012/02/24 06:00
MHDA- 2012/06/01 06:00
CRDT- 2012/02/24 06:00
PHST- 2011/05/04 00:00 [received]
PHST- 2011/06/07 00:00 [revised]
PHST- 2011/12/15 00:00 [revised]
PHST- 2012/01/17 00:00 [accepted]
PHST- 2012/02/24 06:00 [entrez]
PHST- 2012/02/24 06:00 [pubmed]
PHST- 2012/06/01 06:00 [medline]
AID - 10.1111/j.1365-2036.2012.05011.x [doi]
PST - ppublish
SO  - Aliment Pharmacol Ther. 2012 Apr;35(7):745-67. doi: 
      10.1111/j.1365-2036.2012.05011.x. Epub 2012 Feb 22.