Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala², MePhe⁴, Gly(ol)⁵]-enkephalin or DAMGO for MOR, [D-Pen², D-Pen⁵]-enkephalin or DPDPE for DOR, and U-50,488 for KOR, while buprenorphine is a partial agonist for MOR. Antagonists include naloxone or naltrexone as pan antagonists, CTOP as a MOR antagonist, naltrindole as a DOR antagonist, and nor-BNI as a KOR antagonist. The structure of these receptors includes an extracellular N-terminus, seven transmembrane helices, three extracellular and intracellular loops, and a long intracellular amino terminus with glycosylation sites. Sodium ions influence the receptor's constitutive activity and ligand specificity. The receptors can also form homo- and heterodimers, modifying their pharmacological properties.

Opioid receptor signaling is mediated by MOR, DOR, and KOR coupling to the pertussis toxin–sensitive G_i/G_o proteins. Intracellular events include inhibition of adenylate cyclase activity, reduced neurotransmitter release from presynaptic terminals, stimulation of potassium current through GIRKs, and activation of protein kinase C and phospholipase Cβ. Opioids, which act at opioid receptors, can be naturally occurring alkaloids (opiates like morphine, codeine, thebaine, and papaverine) or synthetic compounds. They can be full agonists, partial agonists, or antagonists, depending on their intrinsic activity or efficacy. For example, morphine is a full agonist at the μ-opioid receptor and has a greater binding affinity than codeine. Some opioids can produce both agonist and antagonist effects at different opioid receptors, and their receptor-activating properties and affinities can be manipulated by pharmaceutical chemistry.