Vanoli Emilio, Pentimalli Francesco, Botto Gianluca
Cardiology Section, Department of Molecular Medicine, University of Pavia, Pavia, Italy; Cardiovascular Department, IRCCS Multimedica, Sesto San Giovanni, Italy.
CNS Neurosci Ther. 2014 Jun;20(6):496-502. doi: 10.1111/cns.12283.
Fingolimod is a sphingosine 1-phosphate (S1P) receptor modulator approved to treat relapsing-remitting multiple sclerosis (MS). Initiation of treatment with fingolimod has been found to produce transient bradycardia and/or slowing of atrioventricular impulse conduction in a small proportion of patients. This effect is thought to be due to the interaction of fingolimod with S1P receptors on the surface membrane of atrial myocytes causing a vagomimetic effect, similar to the action of acetylcholine on muscarinic receptors. As a precaution, patients are under electrocardiogram (ECG) monitoring for 6 h after receiving their first dose. Fingolimod is contraindicated in patients with overt or concealed cardiac diseases. However, the Fingolimod Initiation and caRdiac Safety Trial (FIRST), which was designed specifically to investigate the cardiac profile of fingolimod, did not show an increased risk of clinically relevant cardiac events with fingolimod. This review examines the electrophysiology and pathophysiology of cardiac impulse formation in the context of fingolimod. It concludes that these vagomimetic effects should be considered benign and should not prevent the effective use of fingolimod in the treatment of patients with MS.
芬戈莫德是一种已获批准用于治疗复发缓解型多发性硬化症（MS）的鞘氨醇-1-磷酸（S1P）受体调节剂。已发现一小部分患者在开始使用芬戈莫德治疗时会出现短暂性心动过缓和/或房室冲动传导减慢。这种效应被认为是由于芬戈莫德与心房肌细胞表面膜上的S1P受体相互作用，产生拟迷走神经效应，类似于乙酰胆碱对毒蕈碱受体的作用。作为预防措施，患者在接受首剂药物后需接受6小时的心电图（ECG）监测。有明显或隐匿性心脏病的患者禁用芬戈莫德。然而，专门设计用于研究芬戈莫德心脏情况的芬戈莫德起始治疗与心脏安全性试验（FIRST）并未显示使用芬戈莫德会增加临床相关心脏事件的风险。本综述在芬戈莫德的背景下研究了心脏冲动形成的电生理学和病理生理学。结论是这些拟迷走神经效应应被视为良性，不应妨碍芬戈莫德在MS患者治疗中的有效使用。
