Mu-opioid receptor agonists

Mu-opioid receptor agonists

Mu-opioid receptor agonists

Centrally acting opiates

Centrally-acting mu-opioid analgesics are any agents that bind to mu opioid receptors found principally in the central nervous system.1  Centrally acting opiates bind to opioid receptors found principally in the central nervous system. There are four broad classes of opioids: endogenous opioid peptides, produced in the body; opium alkaloids, such as morphine (the prototypical opioid) and codeine; semi-synthetic opioids such as heroin and oxycodone; and fully synthetic opioids such as pethidine and methadone that have structures unrelated to the opium alkaloids.2


The opioids consist of several classes:


  • Antagonists
  • Agonist-antagonist
  • Pure mu-agonist



Antagonists have no analgesic effect. They are used to block the effects of opioid drugs. Antagonist drugs are used to reverse opioid toxicity, typically from overdose. Naloxone, naltrexone and nalmafene are opioid antagonists.



Agonist-antagonists interact with opioid receptors to activate and block their function. Some of agonist-antagonists activate the kappa opioid receptor while blocking the mu receptor. Others interact with the mu receptor and activate it until the dose is increased to the point where the activation-effect plateaus and then drops.


The agonist-antagonist opioid drugs have a ceiling effect above which higher doses produce no additional pain relief. Agonist-antagonist can produce withdrawal in patients who are already receiving another opioid. Some of the agonist-antagonist drugs tend to produce more disorientation compared to pure mu-agonist class. The agonist-antagonist class includes buprenorphine, butorphanol, nalbuphine, and dezocine.


Pure mu-agonists

There is no ceiling dose with pure mu-agonists. In most cases, pain is relieved to an increasing degree as the dose is increased.¬† Side effects may limit therapy. Patients who develop intolerable side effects without achieving satisfactory analgesia are called “poorly responsive” to the specific medication. There is range of variability from patient to patient in the degree of pain relief specific and side effects with regard to specific mu-agonists.


The pure mu-agonists include:

  • Short-acting oral drugs that may be combined with a non-opioid drug and are typically prescribed for acute pain in the outpatient setting. This group includes codeine, hydrocodone, oxycodone, and others.
  • Short-acting drugs that may be given intravenously, subcutaneously or intramuscularly and are usually administered for acute pain in the inpatient setting. This group includes morphine, meperidine, hydromorphone, fentanyl, and others.
  • Long-acting drugs that are usually administered in the outpatient setting for the long-term management of chronic pain. This group includes extended-release oral morphine, extended-release oral oxycodone, extended-release oral hydromorphone, extended-release transdermal (via a skin patch) fentanyl, and methadone.