Effect of the tyramine fragment of opioid receptor ligands on their agonist and antagonist properties

A comparative analysis of correlations between the ED50 and AD50 values describing the agonist and antagonist properties of opioid receptor ligands, on the one hand, and molecular descriptors related to the electronic and geometric properties of the tyramine moiety of these ligands, on the other hand, has been carried out. The affinity of ligands to the complementary site of opioid receptors depends on the electronic properties of the tyramine moiety, such as the basicity of the TF nitrogen atom, the electron-acceptor properties of the "cation head," the electron-donor properties of the aryl moiety, and the ability of substituent atoms in the aryl moiety to act as proton donors and form hydrogen bonds with the OR. The intrinsic activity of ligands depends on the coplanarity of atoms of the substituent in the aryl moiety to the phenyl ring plane. Substantial protrusion of substituent atoms out of the plane of the phenyl ring apparently prevents penetration of a ligand deep into "binding pocket" of the receptor, which leads to disappearance of the antagonist properties of this ligand. © 2006 Springer Science+Business Media, Inc.