Analogues of sparteine. 5. Antiarrhythmic activity of selected N,N'-disubstituted bispidines.

A series of seven N,N'-disubstituted bispidines, structurally analogous to the inner (B and C) rings of sparteine (1) and encompassing a range of lipophilicity in which 1 was centered, has been compared to 1 in regard to antiarrhythmic potency and acute toxicity. Several of the bispidines were of comparable potency, and all but one were somewhat less toxic than 1. The ability of the mononitrate salts of 1 and bispidines 6 and 7 to bind calcium and magnesium cations in Me2SO-d6 solvent has been evaluated by proton magnetic resonance analysis. No binding could be demonstrated under these conditions, which suggested that pharmacologic effects of these compounds may be due to properties other than direct binding of these cations.