Dynorphin A (1-8) analog, E-2078, crosses the blood-brain barrier in rhesus monkeys.

E-2078 is a dynorphin A (1-8) analog, [N-methyl-Tyr1, N-methyl-Arg7-D-Leu8] dynorphin A (1-8) ethylamide. Its ability to cross the blood-brain barrier was examined in rhesus monkeys using matrix-assisted laser desorption/ionization mass spectrometry. In vivo studies were carried out by i.v. injecting E-2078, 10 mg/kg, a dose that had been found to be antinociceptive, to rhesus monkeys. Blood and cerebrospinal fluid samples were collected at various time points after the injection. It was found that E-2078 was stable in vivo in rhesus monkey blood. No biotransformation products were detected in the blood. Mass spectrometric analysis of the cerebrospinal fluid samples collected after E-2078 injection detected the presence of E-2078, indicating that E-2078 had crossed the blood-brain barrier. These findings are consistent with the possibility that systemically administered E-2078 could produce centrally mediated behavioral and physiological effects.