Phe1 Ψ(CH 2-NH)Gly 2]-nociceptin-(1-13)NH 2, a proposed antagonist of the nociceptin receptor, is a potent and stable agonist in the rat spinal cord

Abstract

[Phe 1 Ψ(CH 2-NH)Gly 2]-nociceptin-(1-13)NH 2 is an nociceptin analogue which has been shown to be a selective antagonist of the nociceptin receptor in peripheral tissues. We now report that intrathecal [Phe1 Ψ(CH 2-NH)Gly 2]-nociceptin-(1-13)NH 2 produced a dose-dependent depress ion of the nociceptive flexor reflex in rats. an effect that is similar to nociceptin. The duration of depression produced by [Phe 1 Ψ(CH 2-NH)Gly 2]-nociceptin-(1-13)NH 2 was significantly more prolonged than by nociceptin. The reflex depressive effect of nociceptin was not blocked by [Phe 1 Ψ(CH 2-NH)Gly 2]-nociceptin-(1-13)NH 2. The results indicated that the proposed nociceptin receptor antagonist [Phe 1 Ψ(CH 2-NH)Gly 2]-nociceptin-(1-13)NH 2 is a potent agonist in rat spinal cord and more resistant to enzymatic degradation compared to nociceptin.