NOVEL MET-ENKEPHALIN ANALOG - 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 (war m water tail-flick test), tolerance, cross tolerance to morphine and p hysical dependence. The time course of antinociceptive effect of the c ompound was comparable to morphine. The antinociceptive ED(50) (mu mol kg(-1), i.p.) values for the compound and morphine base were 5.31 and 7.59, respectively. Its antinociceptive effect was blocked by naloxon e, beta-FNA (mu antagonist) and naloxonazine (mu(1) antagonist) but no t 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 m u agonist antinociceptive with a possible weak dependence liability.