Improved delivery through biological membranes. 13. Brain-specific delivery of dopamine with a dihydropyridine in equilibrium with pyridinium salt type redox delivery system.

The dihydropyridine in equilibrium with pyridinium salt type redox delivery system was used for the brain-specific delivery of dopamine. In vivo administration of the catechol-protected dopamine coupled with 1,4-dihydrotrigonelline as the carrier resulted in brain-specific, high and sustained concentrations of the 1-methyl-3-[N-[beta-(3,4-dihydroxyphenyl)ethyl]carbamoyl]pyridinium salt, the direct dopamine precursor, locked in the brain for many hours, while systemic concentration decreased fast, with a t 1/2 of less than 30 min. Significant dopaminergic activity was observed in the brain, which was sustained for hours.