Studies on the structure-activity relationship of 2',6'-dimethyl-l-tyrosine (Dmt) derivatives: bioactivity profile of H-Dmt-NH-CH(3)

Bioorg Med Chem Lett. 2005 Feb 1;15(3):599-602. doi: 10.1016/j.bmcl.2004.11.040.

Abstract

The 2',6'-dimethyl-l-tyrosine (Dmt) enhances receptor affinity, functional bioactivity and in vivo analgesia of opioid peptides. To further investigate its direct influence on these opioid parameters, we developed a series of compounds (H-Dmt-NH-X). Among them, H-Dmt-NH-CH(3) showed the highest affinity (K(i)mu=7.45 nM) equal to that of morphine, partial mu-opioid agonism (E(max)=66.6%) in vitro and a moderate antinociception in mice.

MeSH terms

  • Analgesics / chemical synthesis*
  • Analgesics / pharmacology
  • Animals
  • Dose-Response Relationship, Drug
  • Guinea Pigs
  • Ilium / metabolism
  • Ligands
  • Male
  • Mice
  • Pain / drug therapy
  • Pain / prevention & control
  • Radioligand Assay
  • Receptors, Opioid, delta / antagonists & inhibitors
  • Receptors, Opioid, delta / metabolism
  • Receptors, Opioid, mu / antagonists & inhibitors
  • Receptors, Opioid, mu / metabolism
  • Structure-Activity Relationship
  • Tyrosine / analogs & derivatives*
  • Tyrosine / chemical synthesis*
  • Tyrosine / pharmacology
  • Vas Deferens / metabolism

Substances

  • Analgesics
  • Ligands
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • 2',6'-dimethyltyrosine
  • Tyrosine