Relationship of nonspecific antiarrhythmic and negative inotropic activity with physicochemical parameters of propranolol analogues.

In an attempt to separate the nonspecific antiarrhythmic activity of propranolol from its negative inotropic effects, analogues containing hydrophilic and lipophilic substituents on the nitrogen and on the naphthyl ring were prepared and tested in an isolated tissue preparation. Though it had been predicted that analogues containing a very hydrophilic group on the nitrogen would have the highest antiarrhythmic/negative inotropic effect ratio, it was found that both effects increased identically when the lipophilicity of either the nitrogen or ring substituent was increased.