μ- (mu) and δ – (delta) receptors

mk- (mu) and δ – (delta) receptors are the two main types of opioid receptors in the human body that are part of the complex endogenous opioid system. This system plays a key role in regulating pain, reward, and many other physiological processes.

Both receptors belong to the class of G-protein coupled receptors (GPCRs), and their activation leads mainly to inhibitory effects in the nervous system.

For clarity, here is a comparative table of their main characteristics:

Characteristic	μ-receptor (Mu receptor)	δ-receptor (Delta receptor)
Primary functions	• Analgesia (pain relief) • Euphoria, sense of well-being • Respiratory depression • Constipation • Physical dependence • Sedative effect	• Analgesia (especially in chronic pain) • Mood regulation (antidepressant effect) • Neuroprotection • Modulation of μ-receptor-mediated effects
Endogenous ligands (natural body agents)	β-endorphin (high affinityAffinity is the ability of various cells and tissues to capture and bind certain chemical substances that have entered the body or are formed in it.) Enkephalins (moderate affinity)	Enkephalins (high affinity) β-endorphin (moderate affinity)
Exogenous agonists (external activators)	Morphine, heroin, fentanyl, methadone, oxycodone	Leu-enkephalin, Met-enkephalin (unstable) SNC80 (experimental compound)
Antagonists (blockers)	Naloxone, naltrexone	Naltrindole (experimental)
Key effects upon activation	Potent analgesia, euphoria, respiratory depression (main cause of death in overdose), miosis (pupil constriction), reduced gastrointestinal motility.	Analgesia (less potent but with lower risk of respiratory depression), antidepressant effect, modulation of μ-receptor-mediated responses.
CNS localization	High density in: • Thalamus (pain relay center) • Periaqueductal gray matter (PAG) • Brainstem (respiratory center)	More restricted distribution: • Olfactory bulbs • Neocortex • Limbic system (emotion-related)
Addiction potential	Very high. Primary mediator of the rewarding effects (pleasure/reinforcement) of opioids.	Low. δ-receptor activation alone does not produce significant euphoria or physical dependence.

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Learn more about the mk-receptor (Mu-receptor)

This is the most well-known and clinically significant receptor. It is associated with both the powerful therapeutic effects of opioid analgesics and their main dangerous side effects.

• Role in medicine: It is the main target for morphine and other powerful painkillers used to relieve acute and severe chronic pain (for example, in cancer).
• Side effects:
  • Respiratory depression: The most dangerous effect. mk-agonists reduce the sensitivity of the respiratory center in the brain stem to CO₂. If you overdose, your breathing simply stops.
  • Constipation: Activation of m-receptors in the gut drastically reduces intestinal motility, which is a common problem for patients taking long-term opioids.
  • Euphoria and addiction: A strong sense of pleasure and well-being caused by the activation of m-receptors in the brain’s mesolimbic pathway is a major cause of opioid drug addiction and abuse.

Learn more about the Delta receptor

The role of δ-receptors is less well understood, but no less important. They often work in tandem with m-receptors.

• Prospects for pharmacology: Scientists are actively looking for delta-receptor agonists, as there is evidence that they can provide pain relief with a lower risk of respiratory depression and addiction development. . This could be a breakthrough in creating safe analgesics.
• Influence on mood: Activation of δ-receptors demonstrates antidepressant and anxiolytic (anti-anxiety) effects in preclinical studies.
• Modulation: It is believed that δ-receptors modulate the activity of μ-receptors. For example, blockade of δ-receptors may enhance some of the effects of μ-agonists.

Interaction and meaning

Opioid receptors rarely work in isolation. Their interaction creates a complex regulatory network. For example, some drugs aim to be bifunctional agonists (for example, activate both m-and d-receptors) or agonist-antagonists (block one type and activate the other) to try to separate desirable effects (pain relief) from undesirable ones (respiratory depression, addiction).