Department of Anatomy and Histology, Sydney Medical School, University of Sydney, Sydney, Australia.
Reprod Toxicol. 2012 Nov;34(3):443-50. doi: 10.1016/j.reprotox.2012.06.008. Epub 2012 Jun 28.
This study investigated the effects of antipsychotic drugs on heart function of gestational day (GD) 13 rat embryos in vitro since they all block the I(Kr)/hERG potassium ion channel in addition to their main pharmacological effect on neurotransmitters. The results showed that all the tested antipsychotic drugs caused bradycardia of the rat embryonic heart in a concentration-dependent manner. However, with the possible exception of haloperidol the tested drugs did not cause arrhythmias typically seen with the highly selective I(Kr)/hERG blocking drug dofetilide. For six of the eight drugs tested the effects on the embryonic rat heart were only seen at free drug concentrations that were much greater than those likely to occur in pregnant women taking antipsychotic medication. However, the safety margins for haloperidol and quetiapine were lower.
本研究调查了抗精神病药物对体外妊娠 13 天大鼠胚胎心脏功能的影响，因为除了对神经递质的主要药理作用外，它们还阻断 I(Kr)/hERG 钾离子通道。结果表明，所有测试的抗精神病药物都以浓度依赖的方式导致大鼠胚胎心脏心动过缓。然而，除了氟哌啶醇之外，测试的药物并没有引起与高度选择性 I(Kr)/hERG 阻断药物多非利特一样的心律失常。在测试的八种药物中的六种中，只有在游离药物浓度远高于孕妇服用抗精神病药物时可能出现的浓度时，才会对胚胎大鼠心脏产生影响。然而，氟哌啶醇和喹硫平的安全裕度较低。
