Abstract Some antihistamines (mainly terfenadine and astemizole) have been demonstrated to cause QT interval prolongation and, in some cases, torsade-de-pointes. We investigated the cardiac electrophysiological effects of brompheniramine, a conventional antihistamine. Brompheniramine was reported to prolong QT interval in isolated hearts. To evaluate the electrophysiological effects of brompheniramine, we used whole-cell patch clamp techniques in human ether-a-go-go related gene (hERG)-stably transfected CHO cells, the SCN5A sodium channel transiently transfected CHO cells, and rat myocytes and conventional microelectrode recording techniques in isolated guinea pig papillary muscles. As for the I hERG, the IC 50 value of brompheniramine was found to be 0.90 ± 0.14 μM with a Hill coefficient ( n H) of 1.75 ± 0.42. Action potential duration at 90% repolarization (APD 90) was slightly prolonged by brompheniramine at 10 and 100 μM, but APD 50 was shortened by 100 μM. Moreover, despite the potent hERG current block, reductions of the V max and total amplitude of action potential were observed at high concentrations of brompheniramine. The change in action potential parameters and poor correlations between hERG and APD assay indicated additional effects of brompheniramine on non-hERG channels. In agreement with this hypothesis, the inhibition of I Na (IC 50 values: 21.26 ± 2.52 μM) and I Ca (IC 50 values: 16.12 ± 9.43 μM) by brompheniramine was observed. The results of this study suggest that brompheniramine may possess classes III, Ib and IV properties, especially at high concentrations and that additional studies on non-hERG channels will be necessary to elucidate the complex electrophysiological effects of brompheniramine on the heart.