Potential Organ- or Tumor-Imaging Agents XIX: Radioiodinated Antiarrhythmic Drugs as Potential Myocardial Imaging Agents

Abstract

Iodinated and radioiodinated analogs of propranolol and N,N-dimethylpropranolol were synthesized wherein an iodophenyl moiety replaced the naphthalene ring of the parent drug. These new compounds were evaluated not only for their β-adrenergic blocking and antiarrhythmic activities but also for their ability to accumulate selectively in myocardial tissue. Like propranolol, the iodinated analogs displayed comparable β-blocking and antiarrhythmic activity, and the order of potency was ortho- >meta- >para-iodophenyl. Quaternization of propranolol and the iodinated analogs eliminated the β-adrenergic blocking activity but retained the antiarrhythmic property of the secondary amine precursors. Among the quaternary salts, the antiarrhythmic potency was meta- >ortho- >para-iodophenyl. Tissue distribution of the radioiodinated derivatives revealed that only the quaternary derivatives were selectively accumulated in myocardial tissue. These results demonstrate that an iodophenyl ring can substitute for the naphthalene ring in propranolol and its quaternary salt without significant alteration of pharmacological properties. The radioiodinated quaternary derivatives may be useful pharmacological tools in experiments aimed at relating antiarrhythmic activity to myocardial uptake.