Redox derivatives of tranylcypromine: Syntheses, properties, and monoamine oxidase inhibitor activity of some chemical delivery systems

Several brain‐targeting chemical delivery systems (CDS) based on a dihydropyridine ↔ pyridinium salt type redox system were synthesized for the monoamine oxidase (MAO) inhibitor tranylcypromine (TCP). The dihydronicotinate moiety was chemically attached to the amino group of TCP by either an amide or substituted carbamate linkages. Physicochemical studies of the new derivatives, including chromatographic R_m determinations, were performed. Only the substituted carbamate‐type derivatives manifested an increased lipophilicity relative to the parent compound. In vitro oxidation stability studies were also performed on selected derivatives using a ferricyanide‐mediated method. Results of this assay showed that the dihydropyridine‐type derivatives oxidized to the respective quaternary salt forms with stabilities which empirically correlated with other effective CDSs. Preliminary in vivo studies performed in rats indicated that some of the new derivatives exerted significant biological activity.