This paper describes oxidation of the isoquinoline alkaloid, protopine (PR) at a pyrolytic graphite electrode (PGE) using cyclic and square-wave voltammetry. In the alkaline range (pH 7.5-10.5) of a Britton-Robinson (B-R) buffer, a PR oxidation can be observed as a well-developed voltammetric peak around + 0.9 V (vs. Ag j AgCl j 3 M KCl). With increasing pH of the B-R buffer, the PR peak is shifted to less positive potentials. The acquired voltammetric data suggest that PR strongly adsorbs onto the surface of the pyrolytic graphite where it is subjected to irreversible electrochemical oxidation in its uncharged free (tricyclic) base form. The results are discussed in connection with the electrochemical oxidation of other isoquinoline alkaloids and the potential applications of these data. Protopine (PR) is an isoquinoline alkaloid found in plants of the Fumariaceae, Papaveraceae, Berberidaceae, Ranunculaceae and Rutaceae families. As a whole range of in vitro and in vivo biological activities have been proven for PR and other isoquinolines, plants of the above families are incorporated in several phytopreparations for use in human and veterinary medicine (reviewed in [1][2][3][4]). A molecule of PR includes a dibenz[c,g]azecine system with two methylenedioxy groups localized at C-2,3 and C-9,10 (Scheme 1A) [5][6][7]. This structure is further referred to as a free or tricyclic PR base but this uncharged structural form of the alkaloid can only be observed in an alkaline environment (Scheme 1B). In contrast, in acidic solutions, PR occurs in the form of a tetracyclic cation, PR + (Scheme 1C). Reversible interconversion between free base and the tetracyclic form of PR is related to structural change, transannular interaction between N-7 and C-14, in the 10-member ring B of the molecule (marked in Scheme 1A) [8][9][10][11]. This mechanism is shown in detail at the bottom of Scheme 1 in panels B and C.Currently, over twenty alkaloids whose structure is derived from PR are known (see [1,[12][13][14] and citations therein). The electrochemistry of PR, other protopine alkaloids and their synthetic derivatives and metabolites have not been described to date. Only partial information exists on the reduction of selected isoquinolines at mercury and several papers have focused on their oxidation at a glassy carbon electrode (GCE).