Direct evidence for brain-specific release of dopamine from a redox delivery system

Dopamine (1) was transformed into a lipoidal redox chemical delivery system which crosses the blood brain barrier and is converted to a quaternary ammonium precursor of 1, thus "locking in" this ionized moiety. Systemic administration of this chemical delivery system for 1 increased concentrations of the major acid metabolite of 1, dihydroxyphenylacetic acid, (6) in several brain regions, and despite sustained inhibition of prolactin secretion, concentrations of 1 were unchanged. Inhibition of monoamine oxidase did not encourage the formation of 1 from this delivery system. When de novo synthesis of 1 was inhibited, however, regional brain concentrations of both 1 and dihydroxyphenylacetic acid acid were increased by systemic administration of the delivery system. This study provides direct evidence for the brain-specific delivery of 1 by a redox chemical delivery system and indicates that the 1 formed is delivered to sites which normally store newly biosynthesized 1.