DA-Phen, also known as dopamineâÂÂphenylalanine conjugate, is a synthetic dopamine prodrug which is under preclinical evaluation. Dopamine itself is hydrophilic and is unable to cross the bloodâÂÂbrain 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 (Phe or Phen). It is slowly cleaved by brain enzymes (t<sub>ý</sub> = 460minutes) to yield free dopamine but is also rapidly hydrolyzed in human blood plasma (t<sub>ý</sub> = 28minutes). The drug was intended as a prodrug but may also directly interact with the dopamine D<sub>1</sub>-like and/or D<sub>2</sub>-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.