Table 2.
Experimental drugs for the management of atrial fibrillation. (AF, atrial fibrillation; SK, small-conductance Ca2+-activated K+ channel; SAC, stretch-activated nonselective cation channel; JNK, JUN N-terminal kinase.)
| agent | mechanism of action | description |
|---|---|---|
| MK-0448 | IKur inhibition | effective in preclinical studies, well tolerated in phase 1 clinical trials |
| XEN-D0101 | IKur inhibition | suppresses AF in preclinical studies, does not prolong QT interval in phase1 clinical trials |
| xention-D0103/S66913 | IKur inhibition | effective in preclinical studies, no effect in phase 2 clinical trials, but safe and well tolerated |
| acacetin | multi K+ current blocker: Ito, IKur and IKACh | effective in preclinical studies |
| AP14145 | SK inhibition | effective in preclinical studies and does not prolong QT interval, no clinical trial |
| AP30663 | SK inhibition | effective in preclinical studies, safe and well tolerated in phase 2 clinical trials |
| gadolinium | SAC blocker | effective in preclinical studies |
| ranolazine | multichannel blocker: INa, IKr | atrial selective INa inhibition, significantly reduces clinical AF burden in combination with dronedarone |
| WenXin KeLi | multichannel blocker: INa, Ito, ICa,L | effective in preclinical and clinical studies |
| BMS914392 | IKACh inhibition | ineffective in phase 2 clinical trials, well tolerated and does not affect QTc |
| budiodarone | multichannel blocker: IKur, INa, IKACh,IKr, IKs | effective in preclinical and phase 2 clinical trials, few adverse events |
| ShenSong YangXin capsule | prolongs the atrial effective refractory period, inhibits atrial fibrosis, decreases intracellular iron overload | effective in preclinical and clinical studies |
| vanoxerine | multichannel blocker: INa, IKr, ICa,L | effective in preclinical and phase 2 clinical trials, QT prolongation but no effect on transmural dispersion of repolarization, increased risk of ventricular proarrhythmia in patients with structural heart disease, needs additional studies |
| moxonidine | centrally acting sympathoinhibitory agent | reduces AF burden in hypertensive patients and postablation AF recurrences in hypertensive patients in phase 2 clinical trials, needs additional studies |
| rotigaptide | connexin modulator, prevents the uncoupling of connexin 43-mediated gap-junction communication and normalizes cell-to-cell communication | improvement of conduction velocity does not correlate with AF vulnerability in preclinical studies |
| SP600125 | JNK inhibitor | under preclinical studies |
| dantrolene | RyR2 stabilizer | effective in preclinical studies, no clinical study |
| JTV-519 | multi-ion channel blocker: INa, ICa, IKACh, IKr, IKs; promotes RyR2-FKBP12.6 (calstabin2) binding | effective in preclinical studies, undergoing phase 2 trials for restoration and maintenance of sinus rhythm, and terminates, no data available |