Novel met-enkephalin analogue: A potent systemic mu agonist antinociceptive agent

A new met-enkephalin analogue (compound 82/205) was evaluated for its opioidergic activity in mice. The compound showed antinociception (warm water tail-flick test), tolerance, cross tolerance to morphine and physical dependence. The time course of antinociptive effect of the compound was comparable to morphine. The antinociceptive ED₅₀ (μmol kg^-1 i.p.) values for the compound and morphine base were 5.31 and 7.59, respectively. Its antinociceptive effect was blocked by naloxone, β-FNA (mu antagonist) and naloxonazine (mu₁ antagonist) but not by ICI 174,864 (delta antagonist). Naloxone precipitated withdrawal jumpings were 2.6 times less in compound 82/205 treated mice than the morphine treated group. The new analogue compound 82/205 is a potent mu agonist antinociceptive with a possible weak dependence liability.