Opioid Receptors: Mu, Delta, Kappa

The endogenous system of opioid receptors (μ MOR,κ KOR, and, δ DOR) is well known for its analgesic potential, but each receptor initiates different effects.

Below are quick descriptions of each:

μ-opioid receptor – Wikipedia, the free encyclopedia

The μ-opioid receptors (MOR) are a class of opioid receptors with a high affinity for enkephalins and beta-endorphin, but a low affinity for dynorphins.

They are also referred to as μ-opioid peptide (MOP) receptors. The prototypical μ-opioid receptor agonist is morphine, the primary psychoactive alkaloid in opium


MOR can mediate acute changes in neuronal excitability via suppression of presynaptic release of GABA.

Activation of the μ-opioid receptor by an agonist such as morphine causes


The μ-opioid receptors exist mostly presynaptically in the periaqueductal gray region, and in the superficial dorsal horn of the spinal cord (specifically the substantia gelatinosa of Rolando).

Other areas where they have been located include

Some MORs are also found in the intestinal tract. Activation of these receptors inhibits peristaltic action which causes constipation, a major side effect of μ agonists

δ-opioid receptor – Wikipedia, the free encyclopedia

The δ-opioid receptor, also known as delta opioid receptor or simply delta receptor, abbreviated DOR, is a 7-transmembrane G-protein coupled receptor, that has enkephalins as its endogenous ligands.[3]

The regions of the brain where the δ-opioid receptor is largely expressed vary from species model to species model.

In humans, the δ-opioid receptor is most heavily expressed in the basal ganglia and neocortical regions of the brain;[4] the basal ganglia, which is heavily GABA populated, has been linked to major depressive disorder,[5] suggesting a possible role for the δ-opioid receptor in mood modulation.


The exact role of δ-opioid receptor activation in pain modulation is largely up for debate.

Activation of δ receptors produces analgesia, much more significantly than that of mu-opioid agonists.

However, it seems like mu agonism provides heavy potentiation to any δ-opioid receptor agonism.

Therefore, even selective mu agonists can cause analgesia under the right conditions, whereas others can cause none whatsoever.[6][7]

It is also suggested however that the pain modulated by the mu-opioid receptor and that modulated by the δ-opioid receptor are distinct types, with the assertion that DOR modulates the nociception of chronic pain, while MOR modulates acute pain.[8]

κ-opioid receptor – Wikipedia, the free encyclopedia

The κ-opioid receptor (KOR) is a protein that in humans is encoded by the OPRK1 gene.

The KOR is a type of opioid receptor that binds the opioid peptide dynorphin as the primary endogenous ligand (substrate naturally occurring in the body).[3]

In addition to dynorphin, a variety of natural alkaloids, terpenes and other synthetic ligands bind to the receptor.

The KOR may provide a natural addiction control mechanism, and therefore, drugs that act as agonists and increase activation of this receptor may have therapeutic potential in the treatment of addiction

Below is how receptor bindings function:

Agonists versus antagonists

Not every ligand that binds to a receptor also activates that receptor. The following classes of ligands exist:

  • (Full) agonists are able to activate the receptor and result in a strong biological response. The naturalendogenous ligand with the greatest efficacy for a given receptor is by definition a full agonist (100% efficacy).
  • Partial agonists do not activate receptors with maximal efficacy, even with maximal binding, causing partial responses compared to those of full agonists (efficacy between 0 and 100%).
  • Antagonists bind to receptors but do not activate them. This results in a receptor blockade, inhibiting the binding of agonists and inverse agonists. Receptor antagonists can be competitive (or reversible), and compete with the agonist for the receptor, or they can be irreversible antagonists that form covalent bonds (or extremely high affinity non-covalent bonds) with the receptor and completely block it. The proton pump inhibitor omeprazole is an example of an irreversible antagonist. The effects of irreversible antagonism can only be reversed by synthesis of new receptors.
  • Inverse agonists reduce the activity of receptors by inhibiting their constitutive activity (negative efficacy).
  • Allosteric modulators: They do not bind to the agonist-binding site of the receptor but instead on specific allosteric binding sites, through which they modify the effect of the agonist. For example,benzodiazepines (BZDs) bind to the BZD site on the GABAA receptor and potentiate the effect of endogenous GABA.

Note that the idea of receptor agonism and antagonism only refers to the interaction between receptors and ligands and not to their biological effects.



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