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 antinociceptive effect of the compound was comparable to morphine. The antinociceptive ED50 (mumol 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, beta-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.
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004745:Enkephalins / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017450:Receptors, Opioid, mu / Q000819:agonists*; D013997:Time Factors; D014867:Water
D000700:Analgesics; D004745:Enkephalins; D017450:Receptors, Opioid, mu; C096542:tyrosyl-D-alanyl-glycyl-methylphenylalanyl-N-propylglycinamide; D014867:Water; D004744:Enkephalin, Methionine