Department of Pharmacology and Toxicology, Dresden University of Technology, Dresden, Germany.
Lancet. 2010 Apr 3;375(9721):1212-23. doi: 10.1016/S0140-6736(10)60096-7. Epub 2010 Mar 22.
Inadequacies in current therapies for atrial fibrillation have made new drug development crucial. Conventional antiarrhythmic drugs increase the risk of ventricular proarrhythmia. In drug development, the focus has been on favourable multichannel-blocking profiles, atrial-specific ion-channels, and novel non-channel targets (upstream therapy). Molecular modification of the highly effective multichannel blocker, amiodarone, to improve safety and tolerability has produced promising analogues such as dronedarone, although this drug seems less effective than does amiodarone. Vernakalant, an atrial-selective drug with reduced proarrhythmic risk, might be useful for cardioversion in atrial fibrillation. Ranolazine, another atrial-selective agent initially developed as an antianginal, has efficacy for atrial fibrillation and is being tested in prospective clinical trials. So-called upstream therapy with angiotensin-converting enzyme and angiotensin-receptor inhibitors, statins, or omega-3 fatty acids and fish oil that target atrial remodelling could be effective, but need further clinical validation. We focus on the basic and clinical pharmacology of newly emerging antiarrhythmic drugs and non-traditional approaches such as upstream therapy for atrial fibrillation.
当前治疗心房颤动的方法存在不足，这使得新药的开发变得至关重要。传统的抗心律失常药物会增加室性心律失常的风险。在药物开发中，重点一直放在多通道阻断作用有利、心房特异性离子通道和新型非通道靶点（上游治疗）上。对高效多通道阻滞剂胺碘酮进行分子修饰，以提高安全性和耐受性，已经产生了一些有前途的类似物，如多非利特，但这种药物似乎不如胺碘酮有效。维纳卡兰是一种心房选择性药物，其致心律失常风险降低，可能对心房颤动的转复有用。雷诺嗪最初是作为一种抗心绞痛药物开发的，另一种心房选择性药物，对心房颤动也有疗效，正在前瞻性临床试验中进行测试。针对心房重构的所谓上游治疗，如血管紧张素转换酶抑制剂和血管紧张素受体抑制剂、他汀类药物或ω-3 脂肪酸和鱼油，可能是有效的，但需要进一步的临床验证。我们专注于新出现的抗心律失常药物和非传统方法（如心房颤动的上游治疗）的基础和临床药理学。
