Background and Purpose: Ivabradine is the only FDA-approved HCN channel blocker. This study aims to identify FDA-approved drugs for repurposing as HCN channel blockers, focusing on their effects on hHCN1 channel kinetics, blocking mechanisms, and binding site identification. Experimental Approach: FDA-approved drugs were screened using two criteria: bradycardia as a side effect and structural similarity to known HCN blockers. Selected compounds were docked on hHCN1 channels in closed conformation and open conformation homology model. Based on the established criteria and the additional neuroprotective effects, donepezil was selected for electrophysiological investigation. Molecular docking and site-directed mutagenesis were utilized to determine the residues interacting with donepezil. Key Results: Molecular docking studies on closed conformation of hHCN1 channels showed no binding poses for donepezil inside the pore, while all poses were located within the pore when docked onto the open conformation. Electrophysiological experiments revealed that donepezil effectively blocked hHCN1 channels in dose-dependent manner with a moderate potency, slowed activation kinetics, caused a hyperpolarizing shift in activation curve, and exhibited use-dependent, reversible blockade. Effective blocking required channel cycling between open and closed states. Molecular docking and site-directed mutagenesis identified L357, A383, Y386, and A387 as key residues for binding. Conclusion and Implications: Considering our results and the known neuroprotective effects of donepezil, our findings suggest that donepezil has the potential to be repurposed as a therapeutic hHCN1 channel blocker. This study also highlights the potential of drug repurposing in identifying novel HCN channel inhibitors, paving the way for future drug design targeting HCN channels.