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

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Abstract
A series of 7 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, were compared to 1 in regard to antiarrhythmic potency [mouse chloroform fibrillation assay] and acute toxicity [acute LD50 values i.p. in mice]. Several bispidines were of comparable potency, and all but one were somewhat less toxic than 1. The ability of the mononitrate salts of 1 and 2 bispidines to bind Ca2+ and Mg2+ in Me2SO-d6 solvent was evaluated by PMR analysis. No binding could be demonstrated under these conditions; pharmacologic effects of these compounds may be due to properties other than direct binding of these cations.