Importance of nitrile substitution for the Ca antagonistic action of Verapamil

The effects of verapamil congeners, a) obtained by exchange of the nitrile substituent and b) a structural isomer, on the contractile activity were investigated in isotonically contracting cat papillary muscle. Results indicate that the nitrile substituent is essential for the negative inotropic action of verapamil. Investigations with an ortho disubstituted structural isomer of verapamil showed an unchanged mode of action, while potency is decreased. These findings can be explained on the basis of differences in the steric and electronic properties of the molecules under consideration.