What is the difference between an opiate agonist and antagonist

Full agonist opioids activate the opioid receptors in the brain fully resulting in the full opioid effect. Examples of full agonists are heroin, oxycodone, methadone, hydrocodone, morphine, opium and others.

Partial agonist opioids activate the opioid receptors in the brain, but to a much lesser degree than a full agonist. Buprenorphine is an example of a partial agonist.

Opioid receptors are 7 transmembrane spanning proteins that are coupled to inhibitory G-proteins. When activated, they decrease adenyl cyclase production of the secondary messenger cyclic adenosine monophosphate. This causes a decrease in calcium influx from inhibition of voltage-gated calcium channels and results in the activation of potassium channels, which leads to hyperpolarization.

The hyperpolarized state causes inhibition of neuronal signaling, which in this case inhibits pain transmission. Opioids are classified into categories, depending on receptor binding and affinity Table 3. These classifications are agonist, partial agonist, and antagonist.

There are opioids that have dual agonist and antagonist functions. Full agonists bind tightly to the opioid receptors and undergo significant conformational change to produce maximal effect. Examples of full agonists include codeine, fentanyl, heroin, hydrocodone, methadone, morphine, and oxycodone. Partial agonists cause less conformational change and receptor activation than full agonists.

At low doses, both full and partial agonists may provide similar effects to their full agonist cousins. However, when the dose of partial agonists increases, the analgesic activity will plateau, and further increases in doses will not provide additional relief but may increase the adverse effects. Examples of partial agonists include buprenorphine, butorphanol, and tramadol. Examples include buprenorphine, butorphanol, nalbuphine, and pentazocine. And, some opioids are agonists at 1 or more opioid receptors but also antagonists at other opioid receptors.

Pentazocine is FDA approved and indicated for pain management and formulated with acetaminophen or naloxone. The mechanism of action is partial agonist at the mu opioid receptor and full agonist at the kappa opioid receptor. Although pentazocine weakly antagonizes the analgesic effects of full agonists, it also generates incomplete reversal of behavioral depression, cardiovascular, and respiratory induced via morphine and other full agonists.

Nalbuphine is a synthetic analgesic opioid demonstrating agonist activity at the kappa receptor, while acting as an antagonist at the mu receptor. Nalbuphine has a ceiling effect on respiratory depression at doses greater than 30 mg.

Nalbuphine has been reported to reverse respiratory depression but not analgesia of mu-agonists. Buprenorphine is indicated at high doses for opioid-use disorder while generally at lower doses to treat moderate to severe pain. Buprenorphine has a strong affinity for the mu-receptor causing tight binding and therefore competition at the receptor, displacing other opioids, such as methadone and morphine.

Also, there is incomplete dissociation from the mu-receptor, causing prolonged activity at the receptor. The mu binding affinity of buprenorphine compared with other opioids can be found in Table 5. Of note, buprenorphine has a higher binding affinity compared with naloxone and therefore at higher doses where buprenorphine is most likely to be abused, not readily reversed by naloxone.

It is only at lower doses where there is some competitive binding, and only then should we reasonably expect some reversal by high doses of continuous infusion naloxone. This, of course, begs the question regarding the utility of the combined product, Suboxone. Furthermore, the differential regulation of mu-opioid receptor abundance by agonists and antagonists in immunoblotting assays contrasts with changes in [3H] DAMGO binding.

Taken together, these results suggest that etorphine-induced down-regulation may depend upon mu-opioid receptor degradation and changes in dynaminmediated receptor trafficking. Conversely, antagonist-induced up-regulation does not require an increase in mu-opioid receptor synthesis and may entail conversion of receptors to an appropriate conformation to bind ligand, as well as changes in receptor trafficking.

Abstract Opioid agonists and antagonists can regulate the density of mu-opioid receptors in whole animal and in cell culture. It may act as an agonist for one type of receptor while working as an antagonist for another type of receptor. There are a few medications out there that act as opioid antagonists. All of them listed below are different: one is an agonist, one is a partial antagonist that we use in our outpatient Suboxone clinic! Methadone is a synthetic opioid agonist that eliminates withdrawal symptoms and relieves drug cravings.

It takes the place of other opioid agonists — such as heroin — and attaches to opioid receptors. It does this slowly and does not produce euphoria, so it is safer and does not produce the same addictive effects as other agonists. It has been used successfully for more than 40 years to treat opioid use disorder and must be dispensed through specialized opioid treatment programs.

Buprenorphine is a partial opioid agonist, meaning that it binds to those same opioid receptors but activates them less strongly than full agonists do.

Research has found buprenorphine to be similarly effective as methadone for treating opioid use disorders, as long as it is given at a sufficient dose and for sufficient duration. Naltrexone is a full opioid antagonist, which means that it works by blocking the activation of opioid receptors. Instead of controlling withdrawal and cravings, it treats opioid use disorder by preventing any opioid drug from producing rewarding effects such as euphoria.