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Difference Between Inverse Agonist and Antagonist

June 14, 2021 Posted by Dr.Samanthi

The key difference between inverse agonist and antagonist is that an inverse agonist binds to the same receptor as an agonist but brings about an opposite response to that of an agonist while an antagonist binds to a receptor that will disrupt the interaction and the function of both the agonist and inverse agonist at the receptor.

Receptors are macromolecules involved in chemical signalling within and between cells. The receptors directly or indirectly regulate cellular biochemical processes by binding to specific ligands or drugs. Inverse agonist and antagonist are two types of drugs that interact with receptors in different ways.

CONTENTS

1. Overview and Key Difference
2. What is an Inverse Agonist 
3. What is an Antagonist
4. Similarities – Inverse Agonist and Antagonist
5. Inverse Agonist vs Antagonist in Tabular Form
6. Summary – Inverse Agonist vs Antagonist

What is an Inverse Agonist?

An inverse agonist is a drug that binds to the same receptor as an agonist but brings about an opposite response to that of the agonist. There should be a prerequisite for an inverse agonist action upon a particular receptor. In other words, the receptor must have a constitutive level of activity without any ligand. An agonist augments the activity of a particular receptor above its basal level. An inverse agonist decreases the activity of a receptor below the basal level.

ABAA, muopioid, histamine, melanocortin, and beta-adrenergic receptors have peculiar inverse agonists. For example, the GABAA receptor possesses an agonist such as muscimol that creates a relaxant effect whereas, the inverse agonist for GABAA receptor such as Ro15-4513 creates an agitation effect. Certain beta-carbolines also are inverse agonists for GABAA receptors that create convulsive and anxiogenic effects.

What is an Inverse Agonist

Figure 01: Idealized Dose Response Curve

The two well-known endogenous inverse agonists are the agouti-related peptide (AgRP) and its associated peptide agouti signalling peptide (ASIP) that bind to human melanocortin receptors 4 and 1 (Mc4R and Mc1R) with small-scale affinities. The agonist for this receptor is the hormone α-MSH. AgRP inhibits melanocortin-receptor signalling. These receptors are directly linked to metabolism and body weight control. AgRP acts on the receptor to increase appetite and decrease metabolism and energy expenditure. Moreover, naloxone and naltrexone drugs also act as partial inverse agonists at mu-opioid receptors. Nearly all antihistamines are inverse agonists that are acting at H1 receptors and H2 receptors.

What is an Antagonist?

An antagonist is a drug that binds to a receptor that will disrupt the interaction and the function of both the agonist and inverse agonist at the receptor. Antagonist drugs can interfere with the natural operation of receptor proteins. They are sometimes called blockers such as alpha-blockers, beta-blockers, and calcium channel blockers.

Difference - Agonist vs Antagonist Drugs

Figure 02: Agonist vs Antagonist

The antagonists induce their effects by binding to the active site or another allosteric site on the receptor. The activity of antagonists may be reversible or irreversible. Many antagonists are reversible antagonists. They will bind and unbind a receptor at rates determined by receptor-ligand kinetics. On the other hand, irreversible antagonists covalently bind to the receptor target. They cannot be removed; Phenoxybenzamine is a good example of an irreversible antagonist (alpha-blocker). It permanently binds to α adrenergic receptors and prevents the binding of adrenaline and noradrenaline. Furthermore, antagonists are classified into different types based on their mechanism: competitive antagonists, non-competitive antagonists, uncompetitive antagonists, and silent antagonists.

What are the Similarities Between Inverse Agonist and Antagonist?

  • Both are used in pharmacology as drugs.
  • They both bind to receptors.
  • Both of them can bind to the active site of the receptor.
  • The effects of both of them are against agonists.

What is the Difference Between Inverse Agonist and Antagonist?

An inverse agonist is a drug that binds to the same receptor as an agonist but brings about an opposite response to that of the agonist while an antagonist is a drug that binds to a receptor that will disrupt the interaction and the function of both the agonist and inverse agonist at the receptor. So, this is the key difference between inverse agonist and antagonist. Furthermore, inverse agonist only binds to the receptors that have a constitutive level of activity. In contrast, antagonist binds to both types of receptors that have a constitutive level of activity and ligand-induced activity.

The following infographic presents the difference between inverse agonist and antagonist in tabular form.

Summary – Inverse Agonist vs Antagonist

In biochemistry and pharmacology, receptors are chemical structures composed of proteins. They receive and transduce the signals that may be integrated into biological systems such as cells. The cellular biochemical processes are directly or indirectly regulated by specific receptors. Inverse agonists and antagonists are two types of drugs that interact with receptors in different ways. An inverse agonist binds to the same receptor as an agonist but brings about an opposite response to that of the agonist. On the other hand, the antagonist binds to a receptor that will disrupt the interaction and the function of both the agonist and inverse agonist at the receptor. Thus, this is the summary of the difference between inverse agonist and antagonist.

Reference:

1. “Inverse Agonist.” Overview | ScienceDirect Topics.
2. “Antagonist.” Overview | ScienceDirect Topics.

Image Courtesy:

1. “Inverse agonist 2” By Boghog – Own work (CC0) via Commons Wikimedia
2. “Agonist & Antagonist” By Dolleyj – Own work (CC BY-SA 3.0) via Commons Wikimedia

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Filed Under: Biochemistry

About the Author: Dr.Samanthi

Dr.Samanthi Udayangani holds a B.Sc. Degree in Plant Science, M.Sc. in Molecular and Applied Microbiology, and PhD in Applied Microbiology. Her research interests include Bio-fertilizers, Plant-Microbe Interactions, Molecular Microbiology, Soil Fungi, and Fungal Ecology.

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