A ligand-based 3D pharmacophore model for the μ opioid receptor: application to the morphinan class of opioids

Background Opioid receptors belong to the rhodopsin subclass within the superfamily of G protein-coupled receptors (GPCR), which are characterized by the presence of seven transmembrane (7TM) helices. They interact with morphine and related opioid alkaloids as well as with endogenous opioid peptides. There are three main types of opioid receptors (μ, δ, ), which are differently implicated in opioid function. Ligands specifically targeting each opioid receptor type are of high interest both as research tools and potential therapeutic agents. Activation of the μ opioid receptor produces many other effects, besides its main involvement in pain control, including immunomodulation, respiratory depression, constipation, tolerance and physical dependence. With the lack of an experimental 3D structure of the μ opioid receptor, discovery of 3D pharmacophores for the receptor that can explain the activity of a series of ligands represents an important approach in drug discovery.