Effects of semotiadil fumarate, a novel Ca²⁺ antagonist, on cytosolic Ca²⁺ level and force of contraction in porcine coronary arteries

1 The mechanisms of action of semotiadil fumarate, a novel Ca²⁺ antagonist, were examined by measuring the cytosolic Ca²⁺ level ([Ca²⁺]_i) and force of contraction in porcine coronary arteries, and by determining [³H]‐pyrilamine binding to bovine cerebellar membranes. 2 Semotiadil or verapamil (0.1 and 1 μm) inhibited both the high KCl‐induced increases in [Ca²⁺]_i and force in a concentration‐dependent manner. 3 Histamine (30 μm) produced transient increases followed by sustained increases in [Ca²⁺]_i and force, which were inhibited by semotiadil and verapamil (1 and 10 μm).& The agents were different in that semotiadil reduced the maximum [Ca²⁺]_i and force responses to histamine, but not pD₂ values, whereas verapamil did reduce the pD₂ values for histamine, but not the maximum responses. 4 Verapamil (10 μm), but not semotiadil, inhibited histamine‐induced increases in [Ca²⁺]_i and force in Ca²⁺‐free solution. Neither semotiadil nor verapamil affected the increases in [Ca²⁺]_i and force induced by caffeine. Semotiadil even at the higher concentration (10 μm) did not displace specific binding of [³H]‐pyrilamine to bovine cerebellar membranes. 5 These results suggest that semotiadil inhibits both KCl‐ and histamine‐induced contractions mainly by blocking voltage‐dependent L‐type Ca²⁺ channels. 1995 British Pharmacological Society