Written on November 28, 2022 by Sendra Yang, PharmD, MBA. To give you technically accurate, evidence-based information, content published on the Everlywell blog is reviewed by credentialed professionals with expertise in medical and bioscience fields.
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You may have often heard your healthcare provider refer to a drug as an agonist or antagonist. First, let's distinguish between an agonist and an antagonist and then dig deeper into how an agonist drug works. An agonist is a drug or chemical that binds to a particular receptor on cells in your body [1-3]. A receptor is a protein molecule that is involved in sending chemical signals throughout your body for different responses and functions.
You can think of a protein receptor as a keyhole and an agonist as a key [1-3]. When the key fits the keyhole, the receptor can be activated to work and stimulate a particular response. In this case, an agonist drug will mimic a naturally occurring chemical molecule to fit a specific receptor. The receptor cannot distinguish between the natural chemical and the agonist drug.
In contrast, an antagonist is a drug that binds to the primary protein receptor or elsewhere on the protein to stop the receptor from producing a response [1-3]. Now that you know the critical difference between an agonist and an antagonist drug, we will dig deeper into why agonist drugs are important in medicine and health.
Before the way drugs work was better understood, medicines that were developed in the earlier days had limited specificity or were not as precise as they are today. Some drugs had severe side effects that made their use intolerable. Scientific discoveries and continued work in modern times developed the drug receptor theory . This allowed scientists to describe and understand how drugs and receptor interactions work.
Scientists were able to further appreciate the different types of agonists. Agonists can produce a maximal or partial activation of a receptor [1-3]. You can think of partial agonists as drugs that can bind to a receptor but will only have limited efficacy. Whereas maximal agonists will produce the greatest response with the most effectiveness.
Scientists have developed drug agonists to behave with partial or full efficacy [1-3]. An example of this behavior can be seen in opioid drugs and their effects on the opioid receptors in the brain. Examples of maximal opioid agonists are heroin, oxycodone, morphine, and opium . Methadone is a maximal opioid agonist approved for the treatment of opioid withdrawal, craving prevention, and pain management .
In contrast, partial opioid agonists are buprenorphine, tramadol, butorphanol, or pentazocine . Buprenorphine is a partial opioid agonist used to treat withdrawal and decrease cravings. Buprenorphine activates the opioid receptors in the brain to a lesser extent than methadone.
Both methadone and buprenorphine work by blocking the effects of opioids and are highly effective when used as directed and under supervision by a healthcare provider .
If you thought an agonist drug was interesting, they have another exciting property called an inverse agonist. An agonist drug that binds to a receptor and produces the opposite pharmacological effect that would be made by an agonist is referred to as an inverse agonist [1,2].
For example, if agonism of the receptor leads to hunger, an inverse agonist might cause a lack of appetite [1,2]. So how does this inverse mechanism work? For an inverse agonist response, the receptor activity must have a response. A typical agonist will increase the receptor's action above the standard response threshold. But an inverse agonist will decrease receptor activity below the normal response level. This is what gives an agonism its interesting behavior.
G-protein coupled receptors (GPCR) are good examples of protein receptors that can exhibit an inverse agonism [1,2,4]. GPCR transmits information or signals inside a cell and can be modulated above or below its basal activity levels.
Another example is the ghrelin receptor, known as the growth hormone secretagogue receptor. The ghrelin receptor exerts various physiological functions, including appetite regulation, alcohol consumption, adipocyte metabolism, and glucose homeostasis [1,2,5].
The decades of intense scientific research to understand how agonists affect protein receptors have allowed drug manufacturers to design drugs with varying degrees of specificity to treat human diseases. Consequently, more work is needed to better understand the role of receptor activity in physiological functions and conditions to develop novel drugs. Hopefully, in the coming decades scientists will develop drugs with high selectivity and fewer adverse effects.
If you want to learn more about agonist drugs and how they work, consider talking to your healthcare provider to see if there are agonist medications that are an option for you.
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