Activated ester-carbamate type redox chemical delivery system for improved specific delivery of dopamine to the brain

ABSTRACT

Enhanced central delivery of dopamine [DA] was proposed by application of a dihydropyridine <=> pyridinium salt redox system. the dihydronicotinate moiety was chemically attached to the amino group of dopamine [DA] by a substitued carbamate linkage.this was achieved by acylation of the amino group of DA with chloroethyl chloroformate, followed by condensation with sodium nicotinate under mild conditions. The product was selectively N-alkylated at the pyridine ring and subjected to regioselective reduction to the corresponding 1,4-dihydropyridine derivative. In vitro stability of the prepared chemical delivery system [Dopamine -Chemical Delivery system; DA-CDS2] was studied in phosphate buffer at physiological pH 7.4,acidic as well as at alkaline pH values. Oxidation studies showed that dihydronicotinate is readily converted to the quaternary salt, both chemically and enzymatically. In vivo changes is spontaneous locomotion studies in rat indicated that the new system exerted a significant biological activity