Negative inotropic effects of tiapamil (Ro11-1781) and verapamil in rabbit myocardium

The effects of tiapamil (Ro11-1781) and verapamil on contractility were studied at 1 Hz in isolated rabbit left atrium and right ventricular papillary muscle. The ED50 of tiapamil for the depression of contractility was 33 and 18 times higher than that of verapamil in the former and latter tissue, respectively. In the presence of 100 microM of tiapamil or 10 microM verapamil, the positive staircase phenomenon in papillary muscle was reversed to a negative one. Also, the depression of contractility tended to be less in the first and second responses after a longer interruption of driving stimuli. Both drugs antagonized the inotropic effects of Ca2+ competitively and the pA2 for tiapamil was less than that for verapamil by 1.01. The potency ratios of tiapamil to verapamil for the contractility in this study correspond roughly with those found in clinical use.