Synthesis and biological evaluation of a 13N-labeled opioid peptide.
The 13N-labeled opioid tetrapeptide, Tyr-D-Met(O)-Phe-Gly-[13N]NH2 (SD-62), was synthesized by amidation of its activated p-nitrophenol ester with [13N]ammonia (total synthesis time: 25 min, radiochemical yield: 48%). When injected intravenously into mice, [13N]SD-62 was taken up by the brain and this uptake was blocked by naloxone. In addition, the time course of changes in brain radioactivity paralleled that of the analgesic activity of this compound, suggesting that SD-62 underwent binding to brain opioid receptors. Thus, [13N]SD-62 appears to hold some promise for use as a radiopharmaceutical for in vivo studies of opioid peptide behavior, using positron emission tomography.
Saji
H
H
Department of Radiopharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Tsutsumi
D
D
Kiso
Y
Y
Iimuma
S
S
Mimoto
T
T
Akaji
K
K
Magata
Y
Y
Nakamura
H
H
Kita
A
A
Konishi
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004723:Endorphins / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009270:Naloxone / Q000494:pharmacology; D009590:Nitrogen Radioisotopes; D051381:Rats; D011919:Rats, Inbred Strains; D014055:Tomography, Emission-Computed
D004723:Endorphins; D009590:Nitrogen Radioisotopes; D009270:Naloxone