Agonist vs. Antagonist: What’s the Difference?

Whether you’re taking a medication prescribed by your doctor, buying medicine over the counter, or taking a recreational drug, you probably take the action of the drug for granted and expect it will do what it’s supposed to do. But have you ever wondered - how a blood pressure pill brings down your blood pressure? Or - how does an antidepressant make your mood better?

Drug mechanics are quite incredible, and understanding them has a lot to do with receptors, agonists, and antagonists. Please continue reading to learn more, including the main difference between antagonist & agonist.

What are receptors?

Receptors are protein molecules present on the cell surface in the human body. They receive signals (chemical information) from outside the cell. This information comes from other molecules such as hormones, neurotransmitters, and drugs.

Ligands are molecules inside your body that bind to receptors on a cell and cause a response from that cell, and sometimes other cells as well. Imagine that ligands are keys that fit specific locks, which are receptors.

What are agonists and antagonists?

Agonists and antagonists are two terms commonly used in pharmacology. They refer to drugs or chemical agents that work in opposite ways in terms of how they function and produce effects.

The main difference between agonists and antagonists is that an agonist produces a response by binding to a receptor on the cell. An antagonist opposes the action by binding to the receptor, i.e., it blocks these receptors and renders them ineffective. In other words, the agonists turn the receptors on, and the antagonists turn them off.

Understanding Agonist Drugs

Let’s take a look at agonists in more detail. An agonist can be natural or artificial. Natural agonists are hormones or neurotransmitters. Artificial agonists are drugs that are made to resemble natural agonists. These drugs contain molecules that bind to specific receptors on cells and cause them to become active.

For instance, let’s take opioid receptors in the brain. Endorphins are the natural agonists for opioid receptors. They bind to opioid receptors and produce the effect of pain relief. Therefore, endorphins are natural pain relievers. The pain medication morphine (and the illegal drug heroin) are artificial agonists of opioid receptors. They produce pain relief or a “high” by mimicking the action of the natural agonist.

Another example is serotonin. Serotonin, a natural neurotransmitter or chemical messenger in the brain, is a natural agonist for the 5-HT2A receptors. The synthetic hallucinogenic drug LSD is an artificial agonist of the 5-HT2A receptors.

Agonist drugs are structurally similar to the natural agonists in the human body. They mimic the natural agonists and trigger the receptors, producing the desired response, or in some cases, a much stronger action.

In simple words, you can think of an agonist as a key that fits into a lock (the receptor) and opens a door (produces a chemical reaction or cellular effect). The natural agonist is the master key, but other keys (agonist drugs) can be designed to do the same thing.

Types of Agonist Drugs

There are three main types of agonist drugs:

Complete Agonists

Also called direct binding agonist drugs, they bind directly to the receptor at the same binding site where natural ligands bind. These drugs, therefore, bring about a faster response. Examples of direct agonists include morphine and nicotine. Methadone, which is used to treat opioid addiction, is a full opioid agonist.

Partial Agonists

Also called indirect binding agonist drugs, they promote the binding of the natural ligand to the receptor site. These drugs produce a delayed response. Sometimes, a partial agonist can act as an antagonist by competing for the same receptors as a full agonist. An example is Buprenorphine, a medication used to treat drug addiction to opioids.

Inverse Agonists

An inverse agonist is a drug that produces the opposite effect by binding to a receptor. In other words, an agonist increases the activity of the receptor, whereas an inverse agonist decreases the receptor’s activity below the baseline. For example, an antihistamine medication, an H1 receptor antagonist, has some inverse agonist activity.

Understanding Antagonist Drugs

An antagonist inhibits or opposes the action of an agonist. In other words, an antagonist works by blocking the activity of an agonist. Using the lock and key analogy once more, an antagonist binds to a cell and makes it unable for the agonists to bind to the cell receptor appropriately. As a result, the agonists are rendered ineffective.

To demonstrate how antagonist drugs inhibit the regular action of a receptor, let’s come back to opioid receptors in the brain. As mentioned, heroin is an agonist for the opioid receptor. If someone has taken a potentially fatal heroin overdose, naloxone (an opioid receptor antagonist) can reverse the effects. Naloxone (brand name Narcan) works by blocking or occupying all the opioid receptors, preventing morphine or heroin from binding and activating them. An overdose victim who is unconscious and near death can become fully conscious quite dramatically within seconds of receiving naloxone.

Types of Antagonist Drugs

There are three main types of antagonist drugs:

Competitive Antagonists

These are drugs that bind at the same binding site of the receptor and prevent the natural ligand from binding. The shape of a competitive antagonist mimics the natural ligand. However, if the concentration of the natural ligand increases, it can suppress the effect of a competitive antagonist. Naloxone is a competitive antagonist for the opioid receptor, and it prevents a natural ligand like morphine or heroin from binding to the receptor. Another good example of a competitive antagonist is naltrexone, which is also used to treat opioid addiction.

Noncompetitive Antagonists

A non-competitive antagonist binds at an allosteric site (a site other than the true binding site). The binding of the non-competitive antagonist causes a conformational change (change in shape) of the receptor, which prevents the natural ligand from binding. Ketamine, an anesthetic drug, is a non-competitive antagonist for the NDMA receptor. The difference between competitive and non-competitive antagonists is that the action of the non-competitive antagonist cannot be overcome by the amount of agonist present.

Irreversible Antagonists

Irreversible antagonist drugs bind strongly to the receptor through covalent bonds and cannot be displaced or washed out. They permanently modify the receptor and prevent the binding of the natural ligand.

The Takeaway

The main difference between an agonist and antagonist is that they have opposite actions. An agonist drug always produces a specific action and triggers the receptor to produce a natural response. On the other hand, antagonist drugs block or oppose the natural action or response of a receptor. Some agonists can act as a partial antagonist, but an antagonist drug cannot act as an agonist drug.

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