Comparison of the mode of association of amphiphilic phenothiazine and aza-phenothiazine drugs in aqueous solution

Abstract

The association characteristics in aqueous solution of a 1-aza-phenothiazine derivative, isothipendyl hydrochloride, have been compared with those of a phenothiazine derivative, promethazine hydrochloride, with an identical side chain. The presence of the pyridine-like N atom in the ring system of isothipendyl HCl resulted in a conversion from the typically micellar mode of association observed in solutions of promethazine HCl to a continuous association pattern which was most satisfactorily described by a stepwise association model with association constants, K_N, of equal magnitude. The same model also described the association of another 1-aza-phenothiazine derivative, pipazethate hydrochloride. Addition of electrolyte to solutions of isothipendyl HCl and pipazethate HCl caused an increase in the magnitude of K_N without change in the association pattern.