PMID- 7717857
OWN - NLM
STAT- MEDLINE
DCOM- 19950518
LR  - 20190904
IS  - 0340-5761 (Print)
IS  - 0340-5761 (Linking)
VI  - 69
IP  - 1
DP  - 1994
TI  - Embryotoxic effects of L-691,121, a class III antiarrhythmic agent, in rats.
PG  - 65-71
AB  - L-691,121 is a class III antiarrhythmic agent which blocks potassium currents, 
      leading to prolongation of cardiac potential and prevention of cardiac 
      arrhythmia. In a developmental toxicity study in rats, there was a dose-dependent 
      decrease in embryonic/fetal survival, and death of the entire litter was seen at 
      an oral dose of 0.8 mg/kg per day. The critical period for embryolethality was 
      determined as gestational days (GD) 10-13. In a study where females received 1 
      mg/kg on a critical day (GD 10 or 12) and were killed at 24-h intervals, a high 
      embryonic mortality was seen at 72 h (GD 10 treatment) or 48 h (GD 12 treatment) 
      after dosing. The surviving embryos had morphological abnormalities such as 
      enlarged cardiac tube and pericardium, generalized edema, and hematoma. In order 
      to investigate a possible mechanism for the embryolethality, GD 11 embryos were 
      dissected from females at 4 h after dosing of 1 mg/kg and incubated for 5 h in 
      vitro. The embryonic heart rates were decreased for the first 2 h after 
      incubation but tended to recover to control levels thereafter. When GD 11 embryos 
      were incubated for 4 h with the drug, there were decreases in the heart rates 
      during the entire observation period. In a washout study where the embryos were 
      transferred to drug-free medium after 1-h exposure, decreased heart rates 
      recovered to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Ban, Y
AU  - Ban Y
AD  - Development Research Laboratories, Banyu Pharmaceutical Co., Ltd. Saitama, Japan.
FAU - Konishi, R
AU  - Konishi R
FAU - Kawana, K
AU  - Kawana K
FAU - Nakatsuka, T
AU  - Nakatsuka T
FAU - Fujii, T
AU  - Fujii T
FAU - Manson, J M
AU  - Manson JM
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 0 (Anti-Arrhythmia Agents)
RN  - 0 (Piperidones)
RN  - 0 (Spiro Compounds)
RN  - 136075-61-1 (L 691121)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Anti-Arrhythmia Agents/administration & dosage/*toxicity
MH  - Cardiomegaly/chemically induced
MH  - Dose-Response Relationship, Drug
MH  - Edema/chemically induced
MH  - Embryo, Mammalian/abnormalities/*drug effects/pathology
MH  - Embryonic and Fetal Development/*drug effects
MH  - Female
MH  - Fetal Diseases/chemically induced/mortality
MH  - Gestational Age
MH  - Heart Rate, Fetal/drug effects
MH  - Hematoma/chemically induced
MH  - Male
MH  - Pericardium/drug effects/pathology
MH  - Piperidones/administration & dosage/*toxicity
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Spiro Compounds/administration & dosage/*toxicity
EDAT- 1994/01/01 00:00
MHDA- 1994/01/01 00:01
CRDT- 1994/01/01 00:00
PHST- 1994/01/01 00:00 [pubmed]
PHST- 1994/01/01 00:01 [medline]
PHST- 1994/01/01 00:00 [entrez]
AID - 10.1007/s002040050139 [doi]
PST - ppublish
SO  - Arch Toxicol. 1994;69(1):65-71. doi: 10.1007/s002040050139.