YM758

YM758 is a small molecule inhibitor of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel, specifically targeting the 'funny' (If) current in the sinoatrial node. Developed by Astellas Pharma, it was investigated for the treatment of stable angina pectoris and atrial fibrillation. By inhibiting the If current, YM758 reduces heart rate without significantly affecting myocardial contractility or blood pressure, similar to the mechanism of ivabradine. Clinical development included a Phase 2 trial in Slovakia for stable angina; however, preclinical studies noted extensive accumulation and long-term retention of the compound in the eyeballs and thoracic aorta of rats, which may have impacted its safety profile and further development.