Vol. 282, Issue 2, 633-638, 1997

Dynorphin A (1-8) Analog, E-2078, Crosses the Blood-Brain Barrier in Rhesus Monkeys¹

Jim Yu, Eduardo R. Butelman, James H. Woods, Brian T. Chait and Mary Jeanne Kreek

The Laboratory of the Biology of Addictive Diseases (J.Y., M.J.K.), and the Laboratory of Mass Spectrometry and Gaseous Ion Chemistry (B.T.C.), the Rockefeller University, New York, New York and the Department of Pharmacology (E.R.B., J.H.W.), the University of Michigan, Ann Arbor, Michigan

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.