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

Pharmacol Res. 1995 May;31(5):269-73. doi: 10.1016/1043-6618(95)80031-x.

Abstract

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.

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Binding, Competitive
  • Dose-Response Relationship, Drug
  • Enkephalin, Methionine / analogs & derivatives*
  • Enkephalin, Methionine / pharmacology*
  • Enkephalins / pharmacology*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Receptors, Opioid, mu / agonists*
  • Time Factors
  • Water

Substances

  • Analgesics
  • Enkephalins
  • Receptors, Opioid, mu
  • tyrosyl-D-alanyl-glycyl-methylphenylalanyl-N-propylglycinamide
  • Water
  • Enkephalin, Methionine