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.
D000818:Animals; D001812:Blood-Brain Barrier; D004095:Dihydropyridines; D004298:Dopamine / Q000008:administration & dosage*; D005260:Female; D006207:Half-Life; D008297:Male; D010084:Oxidation-Reduction; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism*; D011726:Pyridinium Compounds / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D004095:Dihydropyridines; D011725:Pyridines; D011726:Pyridinium Compounds; C038806:1,4-dihydropyridine; D011388:Prolactin; D004298:Dopamine