Negative inotropic effect of 3,6-dimethamidodibenzopyriodonium citrate (I-65) on guinea pig papillary muscles

The effects of 3,6-dimethamidodibenzopyriodonium citrate (I-65) on the contractile response of electrically paced guinea pig papillary muscles in vitro were studied. I-65 (0.1-300 mumol/L) decreased the contractile force and inhibited isoprenaline-induced restoration of the contractile response in papillary muscles rendered inexcitable by KCl 22 mmol/L. Both effects were concentration-dependent, and the IC50 were 36.0 and 7.3 mumol/L, respectively. I-65 antagonized the positive inotropic effects of Iso and CaCl2 in a non-competitive manner. Like verapamil, I-65 had a frequency-dependent negative inotropic effect, and delayed the recovery of post-rest potentiation. It is concluded that the negative inotropic effect of I-65 results not only from the reduction of Ca2+-influx through the sarcolemmal membrane, but also from the inhibition of Ca2+ translocation in the sarcoplasmic reticulum.