The antioxidant capacity of some calcium antagonists and one calcium agonist 1,4-dihydropyridines (DHPs) was evaluated by a competitive kinetic procedure. With the exception of Amlodipine, all the calcium antagonist DHPs display an unambiguous antioxidant capacity, while for the calcium agonist DHP (Bay K 8644) no measurable reactivity towards peroxyl radicals could be detected. The finding was corroborated by an electroanalytical investigation of the redox properties of DHPs compounds to get an insight about both the thermodynamic constraints of their oxidation process and reaction pattern. The oxidation potentials decrease with both antioxidant capacity and increasing basic character, thus suggesting the relevance of the electron density on the DHP ring. For all the compounds investigated, the overall oxidation process takes place through a primary one-electron step accompanied by a fast proton release and the formation of a neutral radical undergoing a second much easier one-electron step. The protonated form of the parent pyridine derivative is thus generated as the final product. This pattern is relevant for the antioxidant effect, since the radical intermediate is much more prone to be oxidized than to be reduced, thus fully preventing the propagation of the oxidative chain reaction. In the case of calcium antagonist DHPs, the above release of protons complicates the overall oxidation process by introducing a parasitic side reaction where a coupling between protons and the starting species takes place. This DHP self-protonation subtracts part of the original species from the electrode process because the parent cationic species is no longer electroactive. Conversely, the calcium agonist DHP, which is more difficult to be oxidized, turned out to be such a weak base as to be unable to undergo the self-protonation reaction. The combined effect of oxidation potentials and proton binding capacity of DHPs is a key element for the redox transition, which could support their antioxidant effect and should be considered to some extent in accounting for the calcium antagonist vs calcium agonist effect.
