The interaction of the K+ -sparing agent amiloride — a synthetic chlorinated pyrimidine derivative — with the hASIC1a ion channel is investigated here along homology modeling of the pore region (using the crystal structure of the cASIC1 channel as a template and the known sequence of hASIC1a), automated docking (using the NMR solution structure of amiloride and its conjugated acid, refined by computations), and molecular dynamics simulations. This represents the first modeling and computational chemistry of the pore region of ASIC/DEG/ENaCs/FaNaCh channels. The results agree with the putative amiloride binding site for alphaENaC channel chimeras once the amiloride free base is considered, while its conjugated acid — in contrast with literature beliefs — is poorly scored on a nearby protein pocket. Different protonation conditions of the pore region are irrelevant because histidine residues are far from the binding sites. Mapping the amino acids of the homology model closest to amiloride can have heuristic value in stimulating in silico search of new pore-blocking agents, experimental studies of ASIC channels themselves, and development of code for constant-pH MD simulations.