A number of drugs are largely metabolized after oral administration, especially by redox processes. Among the neuroleptics. loxapine. clotiapine and clozapine. which are sevenmembered tricyclic molé cules with a piperazine sidechain. are known to be extensively metabolized by oxidation. An electrochemical study of thèse compounds was initiated in order to détermine their in vitro redox properties and to elucidate their oxidation mechanisms. The measurements were carried out in aqueous and nonaqueous média using voltammetric, cyclic voltammetric, coulometric. exhaustive electrolysis and thinlayer spectroelectrochemical techniques. The oxidation mechanisms, which differ essentially depending on the pH of the solution, are suggested. In view of thèse results, various similarities have been detected between the in vitro oxidation processes and the pharmacological behaviour reported in the literature. For example, the importance of the piperazine sidechain has been pointed out: oxidation no longer occurs if this sidechain is protonated; similarly, binding to the receptor is prevented if the lone électron pair of the tertiary atom is occupied. Nucleophilic additions have aiso been observed in nonaqueous média and the compounds have been identified using classical spectroscopic techniques. If the oxidation mechanism is identical on the piperazine chain for the three compounds. the process is somewhat différent when it occurs on the tricyclic ring. Loxapine and clotiapine exhibit différent behaviour from clozapine, in their electrochemical as well as in their pharmacological properties.