TASK-1阻害薬doxapramの電気薬理学的作用および抗心房細動作用の解析：イソフルラン麻酔正常犬および慢性房室ブロック犬での検討

• Published in: 日本薬理学会年会要旨集 p. 3-O-111
• Main Authors: 神林, 隆一, 川合, 眞一, 杉山, 篤, 後藤, 愛, 中瀬古（泉）, 寛子, 松本, 明郎, 武井, 義則
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: antiarrhythmic agent; drug efficacy; electrocardiography (ECG); hemodynamics
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.95.0_3-O-111

Introduction: TASK-1 channel, one of the two-pore domain potassium channels, is expressed mainly in the atria, inhibition of which may prolong the action potential duration of atrial myocyte. To investigate whether TASK-1 inhibition suppresses atrial fibrillation (AF), we studied the electropharmacological and anti-AF effects of a selective TASK-1/3 inhibitor doxapram in vivo.Methods: Exp.1) Doxapram hydrochloride hydrate in doses of 0.3 and 3 mg/kg was intravenously administered over 10 min to the isoflurane-anesthetized intact dogs (n=6) to assess the electropharmacological effects. Exp.2) The same doses were infused to the isoflurane-anesthetized, chronic atrioventricular block dogs (n=5) to assess the antiarrhythmic effect against paroxysmal AF induced by 10 s of atrial burst pacing.Results: Exp.1) Doxapram showed positive chronotropic, inotropic and dromotropic effects and delayed the ventricular repolarization, whereas it hardly altered the atrial or ventricular conduction velocity. Doxapram prolonged the atrial effective refractory period (AERP), which did not exhibit frequency dependency. Exp.2) The low and high doses of doxapram tended to rather prolong the AF duration by +22 and +26% from the pre-drug control, respectively.Conclusion: Doxapram did not suppress the paroxysmal AF in vivo, which may be associated with the lack of atrial conduction delay and the less great prolongation of AERP at faster atrial pacing rate. These results suggest that TASK-1 inhibition might have limited efficacy on AF prevention and termination.