Dynorphin A (1-8) analog, E-2078, is stable in human and rhesus monkey blood.
E-2078 is a dynorphin A (1-8) analog, [N-methyl-Tyr1, N-methyl-Arg7-D-Leu8] Dyn A (1-8) ethylamide. Its biochemical stability against enzymatic degradation in vitro in human and rhesus monkey blood, and in vivo in rhesus monkey blood was studied using matrix-assisted laser desorption/ionization mass spectrometry. In vitro studies were carried out in freshly drawn human and rhesus monkey blood, incubated at 37 degrees C for various time periods. In vivo studies were conducted by E-2078 i.v. injection to rhesus monkeys, and blood samples were collected at various time points after the injection. It was found that E-2078 was stable against enzymatic degradation in vitro in freshly drawn human and rhesus monkey blood. Minor biotransformation products from E-2078, such as E (1-4), E (1-5) and E (3-6), were detected in vitro in some human and rhesus monkey blood, but they made up less than 5% of the total starting E-2078 peptide. No biotransformation products were detected in the blood samples from in vivo studies. The apparent half-life of elimination of E-2078 in vivo from the rhesus monkey blood was determined to be 44.0 min.
Yu
J
J
The Laboratory of the Biology of Addictive Diseases, Rockefeller University, New York, New York 10021, USA.
Butelman
E R
ER
Woods
J H
JH
Chait
B T
BT
Kreek
M J
MJ
D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000097:blood* / Q000493:pharmacokinetics; D000818:Animals; D001711:Biotransformation; D004399:Dynorphins / Q000097:blood* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D010446:Peptide Fragments / Q000097:blood* / 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