From the Guidelines
An agonist is a substance that binds to a receptor in the body and triggers a response, mimicking the action of a naturally occurring substance, as seen with opioids binding to mu opioid receptors, resulting in strong analgesia and other effects 1. When an agonist attaches to a receptor, it activates the receptor and produces a biological response similar to or stronger than what would occur with the body's natural chemical messenger. For example, morphine is an agonist that binds to opioid receptors in the brain, producing pain relief and other effects similar to endorphins, which are the body's natural painkillers. Agonists work by fitting into receptor sites like a key in a lock, causing conformational changes that initiate cellular responses. The strength of an agonist's effect depends on both its binding affinity (how strongly it attaches to the receptor) and its efficacy (how effectively it activates the receptor once bound). Some key points to consider about agonists include:
- They can produce a range of effects, from analgesia to euphoria, depending on the receptor they bind to and the individual's response
- They can be used to treat various conditions, such as pain, by enhancing specific physiological processes when the body's natural response is insufficient
- The use of agonists, particularly opioids, requires careful consideration of the potential risks, including addiction and overdose, as highlighted in studies on opioid use and misuse 1
- The management of acute pain in patients receiving opioid agonist therapy, such as methadone or buprenorphine, requires careful consideration of the complex interplay between addictive disease, opioid agonist therapy, and acute pain management 1
From the Research
Definition of an Agonist
- An agonist is a substance that binds to a receptor and triggers a response by the cell [(2,3,4)].
- Agonists can produce distinct signaling outputs when activating the same receptor, leading to different therapeutic or adverse effects 2.
- The efficacy of an agonist is proportional to the sum of probabilities that receptors in individual states activate the cell-signaling pathway 3.
Types of Agonists
- Full agonists produce a maximal response, while partial agonists elicit a lower maximal response [(3,5)].
- Partial agonists may have a lower efficacy due to receptor-related mechanisms, such as conformational states or steric hindrance 3.
- Mixed agonists/antagonists can have mu antagonist (or partial agonist) activity plus kappa agonist and/or sigma agonist activity 5.