PMID- 12220593
OWN - NLM
STAT- MEDLINE
DCOM- 20030224
LR  - 20191025
IS  - 0890-6238 (Print)
IS  - 0890-6238 (Linking)
VI  - 16
IP  - 4
DP  - 2002 Jul-Aug
TI  - Teratogenicity of the I(Kr)-blocker cisapride: relation to embryonic cardiac 
      arrhythmia.
PG  - 333-42
AB  - Cisapride and mosapride are structurally and pharmacologically related prokinetic 
      agents. In contrast to mosapride, cisapride causes embryonic lethality in 
      teratology studies, and has been related to fatal cardiac arrhythmia in the 
      adult. The arrhythmogenic potential of cisapride is linked to its potential to 
      inhibit a specific ion channel (I(Kr)) as a side effect. Mosapride lacks 
      I(Kr)-blocking properties. The aims of this study were (1) to compare the effects 
      of cisapride and mosapride on embryonic heart rhythm in vitro and (2) to 
      investigate if cisapride in vivo, has potential to induce hypoxia-related 
      teratogenic effects as has been shown for selective I(Kr)-blockers. Cisapride 
      induced severe embryonic bradycardia (approximately 60% decrease), and arrhythmia 
      in 94% of the cultured rat embryos at 1000 ng/ml. Mosapride did not induce any 
      bradycardia or arrhythmia up to 2000 ng/ml. In vivo, single dose administration 
      of cisapride to rats on gestational day (GD) 13 caused digital reductions (8/108 
      fetuses, 4/9 litters) at 75 mg/kg and high incidence of embryonic death (55-82%) 
      at 100-200 mg/kg. Identical developmental toxic effects have been described after 
      temporary interruption of oxygen supply, and after single dose administration of 
      selective I(Kr)-blockers, on the same GD. The results support the idea that all 
      potent I(Kr)-blocking agents have the potential to cause embryolethality and 
      teratogenicity, and that the adverse effects are mediated via hypoxic episodes 
      due to embryonic arrhythmia.
CI  - Copyright 2002 Elsevier Science Inc.
FAU - Skold, Anna-Carin
AU  - Skold AC
AD  - Division of Toxicology, Department of Pharmaceutical Biosciences, Uppsala 
      University, Uppsala, Sweden. anna-carin.skold@astrazeneca.com
FAU - Danielsson, Christian
AU  - Danielsson C
FAU - Linder, Bengt
AU  - Linder B
FAU - Danielsson, Bengt R
AU  - Danielsson BR
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Reprod Toxicol
JT  - Reproductive toxicology (Elmsford, N.Y.)
JID - 8803591
RN  - 0 (Benzamides)
RN  - 0 (Gastrointestinal Agents)
RN  - 0 (Morpholines)
RN  - 0 (Potassium Channel Blockers)
RN  - I8MFJ1C0BY (mosapride)
RN  - UVL329170W (Cisapride)
SB  - IM
MH  - *Abnormalities, Drug-Induced
MH  - Administration, Oral
MH  - Animals
MH  - Arrhythmias, Cardiac/*chemically induced/embryology
MH  - Benzamides/administration & dosage/toxicity
MH  - Cisapride/administration & dosage/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Drinking
MH  - Female
MH  - Fetal Heart/*drug effects/physiopathology
MH  - Fetal Hypoxia/chemically induced/physiopathology
MH  - Gastrointestinal Agents/administration & dosage/*toxicity
MH  - Morpholines/administration & dosage/toxicity
MH  - Organ Culture Techniques
MH  - Potassium Channel Blockers/administration & dosage/*toxicity
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2002/09/11 10:00
MHDA- 2003/02/25 04:00
CRDT- 2002/09/11 10:00
PHST- 2002/09/11 10:00 [pubmed]
PHST- 2003/02/25 04:00 [medline]
PHST- 2002/09/11 10:00 [entrez]
AID - S0890623802000424 [pii]
AID - 10.1016/s0890-6238(02)00042-4 [doi]
PST - ppublish
SO  - Reprod Toxicol. 2002 Jul-Aug;16(4):333-42. doi: 10.1016/s0890-6238(02)00042-4.