Mechanical and energetic effects of 2-n-butyl-3-dimethylamino-5,6-methylenedioxyindene (2-butyl-MDI) were investigated in isolated frog semitendinosus muscles at 0 degrees C. Previous research on various tissues suggested that this compound functions as an intracellular Ca2+ antagonist. The effects of 2-butyl-MDI (2 X 10(-4) M) with respect to time were progressive and reversible with exposures of 30 min or less. A 30-min exposure to the agent significantly decreased twitch and tetanus force and energy liberation, increased the twitch-to-tetanus ratio, prolonged kinetics of force development, induced a stimulus frequency-dependent tetanic fatigue, and decreased contractile economy (measured as force per unit energy liberation). Energy associated with Ca2+ cycling, activation heat, was depressed by 31 +/- 4%. The significant reduction of activation heat production by 2-butyl-MDI suggests that the quantity of Ca2+ released by the sarcoplasmic reticulum upon stimulation is reduced. However, the complexity of the results summarized above suggests multiple sites and/or modes of action for the agent.