Opioids: Mechanism of Action, Tolerance, Toxicity and Addiction

Abstract

Opioids are the most effective and widely used drugs in the treatment of severe pain. They act through G protein-coupled receptors. Four families of endogenous ligands (opioid peptides) are known. The standard exogenous opioid analgesic is morphine. Opioid agonists can activate central and peripheral opioid receptors. Three classes of opioid receptors (μ, δ, κ) have been identified.Multiple pathways of opioid receptor signaling (e.g., Gi/o coupling, cAMP inhibition, Ca++ channel inhibition) have been described. Early binding studies and bioassays defined three types of opioid receptors (Lord et al., 1977), the μ-, δ- and κ receptors.Anumber of other receptor types have been proposed (e.g., sigma, epsilon, orphanin) but are currently not considered “classical” opioid receptors (Kieffer and Gaveriaux-Ruff, 2002). The identification of opioid receptor complementary DNA (cDNA) allowed for the in