Cyclic voltammetric study of some calcium antagonist dihydropyridines in aqueous medium

Abstract

The electrochemical behavior of several calcium antagonists of the dihydropyridine family has been investigated in aqueous buffered solution using a glassy carbon electrode. Both oxidation of the dihydropyridine ring and the reduction of the nitro or benzoxadiazole moiety are observed using cyclic voltammetry and the shape of the voltammograms depending on the initial scan direction. Each process may interfere with the other. The single reduction peak corresponds to a four-electron transfer giving rise to the hydroxylamine. Reversing the scan leads to the nitroso derivative, its reversibility depends on the 2-or 3-position of the nitro group. Oxidation of the dihydropyridine ring proceeds through a two-electron exchange. However, nicardipine, which possesses a dialkylbenzylamine side chain, exhibits two additional peaks; the first due to the methoxylation of the side chain, and the second attributed to the oxidative chlorination of this moiety. Potentials are pH dependent. A general EC mechanism is proposed for the overall process.KEY WORDS: Dihydropyridine, cyclic voltammetry, nicardipine, calcium antagonists. lK?RODUCTIONNifedipine and nicardipine, and more recently, nitrendipine, felodipine, and isradipine belong to the dihydropyridine derivatives known as calcium antagonists or calcium entry blockers. These drugs inhibit the transport of calcium ions across membranes of the cardiovascular system's cells, producing a vasodilatation effect [ 1-31, Nifedipine and nicardipine have been proposed together with p-blockers and nitrates for the treatment of angina pectoris and hypertension [4,5], while the three others are more specifically indicated against essential hypertension [5-81. These last three compounds exhibit lower adverse effects [5], greater vascular selectivity [l], and also improved kinetic qualities with half-lives of about 8 hours [ 9-1 11, while nifedipine and nicardipine have shorter halflives (3 hours) [12][13][14].Dihydropyridine derivatives undergo rapid and extensive hepatic oxidative metabolization by Cytochrome This paper is dedicated to the memory of Professor Gaston J. Patriarche. 'To whom correspondence should be addressed. P 450 enzymes [15,16], giving rise to pyridine analogs that are pharmacologically inactive and further biotransformation including ester cleavage [ 17, 181.These drugs are more or less light sensitive. Their degradation pathways depends on the kind of irradiation; UV light gives rise to the nitropyridine derivative while visible light produces the nitrosopyridine analog [19][20][21][22].Owing to the low levels to be determined in biological fluids for pharmacological investigations (in the 0.1-5 ng-ml-' range), mainly chromatographic methods have been developed, including gas [23-251 and liquid techniques 129, 25-28]. A radioimmunoassay has also been proposed [ 291. However, since pharmacological activity and metabolization are related to redox processes on the dihydropyridine moiety [30, 311, the knowledge 9f the voltammetric behavior of these compounds is of ...

Voltammetric Determination of Antibacterial Nitro‐Compounds at Activated Carbon Fibre Microelectrodes

“…A single peak whose E p shifted to more negative values as pH increased was observed for all the compounds tested. This dependence of the cathodic potential on pH is in agreement with the electrochemical reduction of the nitro group to give the corresponding hydroxylamine by exchange of four electrons and four protons [19,25]. Moreover, in all cases the E p vs. pH plots showed two linear ranges with different slope values that intercepted at pH 7.4 (NFA), 7.7 (NFZ) and 8.1 (MNZ), which should correspond to the pK a values of these compounds.…”

“…Accordingly with the currently accepted mechanism [25,19], the cathodic responses can be attributed to a fourelectron reduction of the nitro group to give the hydroxylamine derivative. The peak potentials values obtained at the activated CFMEs were less negative than those reported at bare and enzyme-modified carbon paste electrodes [21] and at activated and non-activated glassy carbon electrodes [19,20].…”

Voltammetric Determination of Tinidazole Using a Glassy Carbon Electrode Modified with Single-Wall Carbon Nanotubes

“…Upon a reverse scan, no corresponding oxidation peak is observed, revealing that the electrode reaction of tinidazole is totally irreversible. According to the currently accepted mechanism for the electroreduction of aromatic and heteroaromatic nitro compounds, the reduction peak is attributed to a four-electron reduction of the nitro group to the corresponding hydroxylamine, 15,16 and may be written as follows:…”

Redox properties of isradipine and its electrochemical detection in the HPLC determination of the compound in human serum

“…Based on the results obtained by cyclic voltammetry, controlled potential electrolysis, spectroelectrochemistry and from previous literatures (Bratin and Kissinger, 1982;Morales et al, 1987;El-Jammal et al, 1992) concerning the voltammetric and polarographic studies of similar compounds, the following peak correspondence could be proposed.…”

“…The Redox behavior of the members of the dihydropyridine group was studied by Sankar and Reddy (1990), Hazard et al (1991), Ellaithy and Zuman (1992), Sqella et al (1998Sqella et al ( , 1989Sqella et al ( , 1990Sqella et al ( , 1991Sqella et al ( , 1992a and Takamura et al (1995a,b). Voltammetry of isradipine was performed by El-Jammal et al (1992). The main redox positions of these compounds are the dihydropyridine ring and the aromatic nitrogen group.…”