Interaction of formamidines with the platelet 5-hydroxytryptamine uptake system

1. The activity of the insecticide/acaricide N'-(4-chloro-o-tolyl)-N,N-dimethylformamidine (chlordimeform), its two formamidine metabolites, N'-(4-chloro-o-tolyl)-N-methylformamidine (demethylchlordimeform) and N'(4-chloro-o-tolyl) formamidine (didemethylchlordimeform), and 116 other formamidines and related compounds as inhibitors of rat platelet 5-hydroxytryptamine (5-HT) uptake was studied. Though several formamidines were more active than chlordimeform (pI50 3.9), none was as potent as imipramine. Didemethylchlordimeform (pI50 4.4) was the most potent formamidine examined. 2. Inhibition of 5-HT uptake by chlordimeform was mixed. Moreover, chlordimeform inhibition of 5-HT uptake by reserpinized platelets was not significantly different from uptake by non-reserpinized platelets. 3. Chlordimeform and its two formamidine metabolites caused release of platelet 5-HT, and their potency as releasers paralleled their activity as uptake inhibitors. 4. Electron microscopy indicated that chlordimeform treatment changed platelet shape and size but apparently did not alter physical integrity of the membrane. 5. It was suggested that platelet 5-HT storage vesicles were the most probable site of formamidine action.