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.
Yu
J
J
The Laboratory of the Biology of Addictive Diseases, the Rockefeller University, New York, New York 10021, USA.
Butelman
E R
ER
Woods
J H
JH
Chait
B T
BT
Kreek
M J
MJ
D018712:Analgesics, Non-Narcotic / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D000818:Animals; D001711:Biotransformation; D001812:Blood-Brain Barrier; D004399:Dynorphins / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D004906:Erythrocyte Count; D005260:Female; D008253:Macaca mulatta; D008297:Male; D010446:Peptide Fragments / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D012015:Reference Standards; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D018712:Analgesics, Non-Narcotic; D010446:Peptide Fragments; C061285:E 2078; D004399:Dynorphins