2-Minute Neuroscience: Agonism, Antagonism, & Allosteric Modulation

Drugs can interact with receptors in a number of different ways, which are typically categorized as various types of agonism, antagonism, or allosteric modulation. In this video, I describe these drug-receptor interactions.

TRANSCRIPT:

Agonism occurs when a drug binds to a receptor and causes a biological response. Agonist drugs typically bind to the same place on the receptor as the substance that naturally activates the receptor, or the endogenous agonist. Agonists that can generate a maximal response at a receptor are called full agonists. Partial agonists are only able to generate a fraction of the possible response at a receptor. In some cases, an agonist may bind to a receptor and cause a decrease in signaling at that receptor. These substances are called inverse agonists, and they can produce effects that are opposite to those of an agonist.

Receptor antagonism occurs when a drug binds to a receptor but does not activate the receptor; in the process, it interferes with the ability of agonists to activate the receptor. The most common type of antagonism is reversible competitive antagonism, where a drug competes with an agonist for its binding site, in the process limiting the amount of agonist that can bind to the receptor at the same time. Reversible competitive antagonists frequently unbind and rebind to receptors. An agonist can replace the antagonist while it is unbound, allowing the antagonist’s effects to be overcome with the addition of more agonist. Irreversible competitive antagonists, sometimes called non-competitive antagonists, also bind to the site where an agonist binds but unbind from the receptor very slowly, if at all. They can reduce the maximal effect an agonist has, regardless of how much agonist is present.

Some drugs may bind to a receptor at a different site from where an agonist binds and influence the function of the receptor. These drugs, often called allosteric modulators, may increase or decrease the likelihood of an agonist binding to a receptor, enhance or reduce the effects an agonist has when it does bind, or activate the receptor on their own.

References:

Neubig RR, Spedding M, Kenakin T, Christopoulos A; International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacol Rev. 2003 Dec;55(4):597-606.

Ritter JM, Flower R, Henderson G, Loke YK, MacEwan D, Rang HP. Rang & Dale's Pharmacology. 9th ed. New York, NY: Elsevier; 2020.

[science_and_anonymous]

I love this YouTube channel. I just found it, and it's become my new addiction

[grndragon]

Im not in school or have a test. Im just curious.

[aamirrazak]

Nice video as always antagonists remind me of inhibitors for enzymes in their mechanisms of action

[VectormanX]

how can someone upregulate receptors, are auto regulated by the absence of chemicals?i mean if you had low dopamine for some time are the receptors become more sensitive by the time to balance the low quantity of the chemicals?

[HeatherWP]

I’m wondering if you (or anyone who might read this comment) are able to help me make sense of the repeated use of, for instance, Acetylcholine antagonists in people with dementia? Particularly when they are known to have low ACh?

[anastasia..]

What is the difference between an inverse agonist and an irreversible competitive antagonist?

[natalief]

How does this work with something like a GABA supplement? Is it an agonist or antagonist or neither?

[johanaquewbu]

How do partial agonists produce a fraction of the possible response? Does this mean they cause changes in the receptor that favour the activated state but don't fully activate it?

[stijnhelmer]

Hi, would be amazing if you respond: when you say a ''drug'' binds to a receptor (for agonism aswell as antagonism), do you mean a medicine, or just any type of ligand that can bind to a receptor? Thanks in advance! (if anyone in the comments knows lmk)

[savannahhayes]

Are antagonists only used to block the agonists of other drugs/substances, or are they taken to stop naturally occurring processes as well?