Original Article: PDF OnlyBorowicz Luanne E.; Schniepp, Henry C.; Sanguinetti, Michael C.Journal of Cardiovascular Pharmacology: January 1987 - p 57-64 Free Abstract Summary: The in vitro electrophysiological properties of a new class I antiarrhythmic agent, SC-36602, were evaluated by recording action potentials (APs) from guinea pig papillary muscle. SC-36602 and its (+) and (−) enantiomers (10−6−10−4M) caused a concentration- and only slight frequency-dependent depression of Vmax (maximum rate of rise of the AP). At stimulation rates of 30, 60, 120, and 200 pulses/min, SC-36602 (10−4M) reduced Vmax to 64 ± 2.2, 62 ± 2.8, 60 ± 2.4, and 58 ± 2.7% of control, respectively, and significantly shortened effective refractory period (ERP) (20–40%). The rate constants for onset of block of Vmax during trains of stimuli at 1 or 3.3 Hz were similar (˜0.2 AP−1). Slow recovery from Vmax block following a stimulus train recorded in tissue depolarized by 10 mM [K+]o Tyrode's solution was enhanced following exposure to SC-36602. The normalized relationship between Vmax and membrane potential was shifted 3 and 12 mV in the hyperpolarizing direction at stimulation frequencies of 0.2 and 1 Hz, respectively. These results suggest that SC-36602 would preferentially depress conduction in depolarized tissue in vivo. © Lippincott-Raven Publishers.