title: Antipsychotic drugs cause bradycardia in GD 13 rat embryos in vitro.
abstract: 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.
authors: Department of Anatomy and Histology, Sydney Medical School, University of Sydney, Sydney, Australia.
authors: M
authors: M
authors: Gunnström
authors: D
authors: D
authors: Ababneh
authors: W S
authors: WS
authors: Webster
authors: D
authors: D
authors: Oakes
authors: H
authors: H
authors: Ritchie
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001919:Bradycardia / Q000139:chemically induced* / Q000503:physiopathology; D000072237:ERG1 Potassium Channel; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000502:physiology; D026902:Potassium Channel Blockers / Q000009:adverse effects*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000009:adverse effects*
chemical_list: D014150:Antipsychotic Agents; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D062554:NAV1.5 Voltage-Gated Sodium Channel; D026902:Potassium Channel Blockers; C568322:Scn5a protein, rat; D026941:Sodium Channel Blockers