From the Guidelines
An agonist is a substance that binds to a receptor and activates it, producing a biological response similar to the body's natural signaling molecules, as seen with opioid agonists that bind to mu opioid receptors, resulting in strong analgesia and various other physiological effects 1. When an agonist attaches to its target receptor, it mimics the action of endogenous ligands, triggering the same cellular pathways and physiological effects. The key characteristic of agonists is their ability to initiate a response, unlike antagonists which block receptors without activating them. Some key points about agonists include:
- Agonists vary in their efficacy (the maximum response they can produce) and potency (the amount needed to achieve an effect) 1.
- Full agonists can produce the maximum possible response, while partial agonists generate only a fraction of that response even at saturating concentrations.
- The effectiveness of agonist medications depends on both their binding affinity for the target receptor and their intrinsic activity once bound.
- Agonists are valuable as medications across many therapeutic areas, including pain management (opioid agonists like morphine), asthma treatment (beta-2 adrenergic agonists like albuterol), and Parkinson's disease (dopamine agonists like ropinirole) 1. The most recent and highest quality study on this topic is from 2021, which highlights the importance of understanding the mechanism of action of agonists, particularly opioid agonists, in order to optimize their use in clinical practice 1.
From the FDA Drug Label
Morphine is a full opioid agonist and is relatively selective for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The characteristics of an agonist, such as morphine, include:
- Binding to specific receptors: Morphine binds to opioid receptors, specifically the mu-opioid receptor.
- Activation of the receptor: As a full opioid agonist, morphine activates the receptor, producing a response.
- No ceiling effect: There is no maximum limit to the effect of morphine, as it continues to produce analgesia as the dose is increased, limited only by adverse reactions 2.
- Production of a therapeutic effect: The principal therapeutic action of morphine is analgesia.
From the Research
Characteristics of an Agonist
- An agonist is a substance that binds to a receptor and activates it, producing a biological response 3, 4, 5, 6, 7
- Agonists can be classified as full agonists, partial agonists, or inverse agonists, depending on their ability to activate the receptor and produce a maximal response 4, 5, 6
- The efficacy of an agonist is a measure of its ability to produce a biological response, and it is proportional to the sum of probabilities that receptors in individual states activate the cell-signaling pathway 4, 7
- Agonists can also exhibit biased agonism, where they selectively activate certain signaling pathways over others, which can affect their therapeutic and adverse effects 3, 6
Mechanisms of Agonist Action
- Agonists can bind to receptors in multiple conformational states, which can affect their ability to activate the receptor and produce a biological response 4
- The binding of an agonist to a receptor can also induce a conformational change in the receptor, which can affect its ability to activate downstream signaling pathways 4, 6
- Agonists can also interact with other molecules, such as G proteins and beta-arrestins, which can affect their ability to activate signaling pathways and produce biological responses 6, 7
Types of Agonists
- Full agonists are substances that bind to a receptor and produce a maximal biological response 4, 5
- Partial agonists are substances that bind to a receptor and produce a submaximal biological response 4, 5, 7
- Inverse agonists are substances that bind to a receptor and produce an opposite biological response to that of a full agonist 4