DA-Phen
DA-Phen, also known as dopamine–phenylalanine conjugate, is a synthetic dopamine prodrug which is under preclinical evaluation. Dopamine itself is hydrophilic and is unable to cross the blood–brain barrier, thus showing peripheral selectivity. DA-Phen was developed as a dopamine prodrug that would allow for entry into the central nervous system via passive diffusion and/or active transport.
DA-Phen is a conjugate of dopamine and the amino acid phenylalanine. It is slowly cleaved by brain enzymes to yield free dopamine but is also rapidly hydrolyzed in human blood plasma. The drug was intended as a prodrug but may also directly interact with the dopamine D1-like and/or D2-like receptors. DA-Phen has shown centrally mediated effects in animals, including increased cognitive flexibility, improved spatial learning and memory, antidepressant- and anxiolytic-like effects, and decreased ethanol intake.
Other analogues, such as DA-Trp and DA-Leu, have also been developed and studied.