Opioid Receptors

Study Notes

There are three known types of receptors for opioid analgesics: μ, κ, and δ.
κ-Opioid receptors are involved in analgesia, but also produce nausea and dysphoria (sadness, irritability, anxiety).

δ-Receptor activation produces analgesia and may be related to seizures.
Endogenous ligands for the δ receptor are the enkephalins.
Until recently, there were few pharmacological tools for studying δ receptors, limiting understanding of their function.

Exogenous ligands that activate δ receptors mimic the phenomenon of 'ischemic preconditioning', protecting downstream tissues from permanent interruption of blood supply.
In rat models, introduction of δ-active ligands results in significant cardioprotection.

Opioid receptors are a group of G-protein coupled receptors with opioids as ligands.
Endogenous opioids include dynorphins, enkephalins, and endorphins.
Opioid receptors share ~40% identity with somatostatin receptors (SSTRs).

Activation of the μ receptor by an agonist like morphine causes analgesia, sedation, reduced blood pressure, itching, nausea, euphoria, decreased respiration, miosis (constricted pupils), and decreased bowel motility leading to constipation.
Effects like sedation, euphoria, and decreased respiration tend to disappear with continued use as tolerance develops.
Analgesia, miosis, and reduced bowel motility tend to persist with little tolerance development.
Tolerance develops to different effects at different rates due to activation of different μ-receptor subtypes.
μ1-Receptors block pain, while μ2-receptors cause respiratory depression and constipation.