BMS 123 · Common Core (Tronc commun)Section 5.5 · Pharmacodynamics: mechanisms and receptors

Section 22 of 27

Agonists and antagonists

Distinguish full, partial, competitive, non-competitive and mixed agonists and antagonists, and explain what receptor selectivity means in practice.

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Why this matters

Almost every therapeutic decision comes down to whether you want to switch a receptor on or keep it off, and whether you need an effect that can be reversed quickly. Competitive and non-competitive antagonists look similar in a drug list but behave completely differently when a patient deteriorates: one can be overcome, the other cannot. Recognising which is which is a safety skill, not an academic one.

What you need to know first

You need affinity and intrinsic activity from 5.4, and the idea that a drug–receptor complex is reversible unless a covalent bond forms. Dose–response curves are used here only in words; their calculation is the subject of Unit 6.

Words to know (6)

Full agonist: A drug that combines with its receptor and produces the maximal response obtainable, even at low concentration. Morphine produces maximal analgesia through opioid receptors.
Partial agonist: A drug that binds weakly, activates the receptor and produces a sub-maximal effect regardless of the concentration. A partial agonist cannot reach the maximal response of a full agonist.
Competitive antagonist: A drug that binds reversibly to the same receptor as the agonist and competes with it for the same site. Its effect is surmountable by increasing the agonist concentration.
Non-competitive antagonist: A drug that binds irreversibly, usually covalently, and blocks activation that cannot be overcome by more agonist. Such drugs are used in experiments and in chemotherapy.
Mixed agonist–antagonist: A drug that acts as an agonist on one set of receptors and as an antagonist on another set at the same time. Some analgesics act this way on different opioid receptor types.
Receptor selectivity: The relative preference of a drug for one receptor subtype over others, which is never absolute. Salbutamol prefers β₂ receptors but also touches β₁.

One idea at a timeIdea 1 / 6

In one sentence A full agonist combines with its specific receptor and produces the maximal response obtainable, with high potency and high efficacy.

Full agonist: maximal response even at low concentration

A full agonist is a drug that combines with its specific receptor to produce the maximal effect or response obtainable. Full agonists elicit maximal effects even at low concentrations, so both their potency and their efficacy are high. This is the reference against which other drugs acting on the same receptor are judged: any drug that can never reach the same maximal response is not a full agonist, whatever dose is given. Full agonists are the drugs that imitate the body’s own signal most completely, which is why they are used when a physiological function has to be restored rather than merely restrained.

For example

Morphine produces strong analgesia through opioid receptors even at low doses, whereas aspirin needs a much larger dose for a weaker effect. Weight for weight, the full agonist is far more potent as well as more efficacious.

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Why is a full agonist described as both potent and efficacious?

Show the answer

Because it produces the maximal obtainable response, which is efficacy, and it does so even at low concentration, which is potency.

Read detailed explanations

Why a partial agonist can behave like an antagonist: The behaviour of a partial agonist depends on what else is present at the receptor. When it is given alone, it produces a steady sub-maximal response, which can be exactly what is wanted if the aim is to activate a system gently. When it is given together with a full agonist, the picture changes. Both molecules compete for the same binding site, and every receptor that the partial agonist occupies is one that the full agonist can no longer occupy. Because the partial agonist activates that receptor less strongly than the full agonist would, the total response falls. The partial agonist has therefore produced a functional antagonism without any covalent bond and without any change in the receptor. This is not a laboratory curiosity. It explains why a partial agonist can both treat a condition and blunt the effect of a rescue medicine given at the same time, and why the order and timing of the two drugs can change the clinical result. It is also a useful reminder that the words agonist and antagonist describe behaviour rather than molecules: the same molecule can be either, depending on what it is competing with.
Surmountable and insurmountable blockade at the bedside: The difference between the two kinds of antagonism is not academic, because it decides what you can do when a patient deteriorates. Suppose a patient is over-blocked by an antagonist and needs the receptor activated again. If the antagonist is competitive, the receptors are still there and the antagonist is still reversibly bound: raising the concentration of the agonist displaces it, and the response returns. That is why competitive antagonists are described as clinically useful — the block can be tuned, reduced by stopping the drug, or outweighed by an agonist. If the antagonist is non-competitive, the receptors it has bound are permanently modified or removed from the pool. Adding agonist has nowhere to bind, so the response stays low, and the only route back is for the body to synthesise new receptor protein, which takes time. This is exactly why such drugs are largely reserved for experiments and for chemotherapy, where a long, irreversible effect is the therapeutic goal. It also explains the practical rule that a patient’s response to a competitive antagonist can be predicted from the agonist concentration available, whereas the response to a non-competitive antagonist depends on how much receptor protein remains and on how fast it is replaced.

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Agonists and antagonists compared

Five patterns of action on the same receptor, with the shape each one gives to a dose–response curve: full, partial, mixed, competitive block and non-competitive block.

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01 / 5Full agonist

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Full agonist

A drug that combines with its specific receptor and produces the maximal response obtainable. It elicits maximal effects even at low concentrations, so both its potency and its efficacy are high. Morphine acting on opioid receptors is the classic example.

Schematic, not to scale. The curves are drawn by hand to show shape, not measured data; real curves are plotted from experiments and their positions depend on the tissue as well as on the drug.

Key points to remember

A full agonist produces the maximal response obtainable, even at low concentration.
A partial agonist binds weakly and produces a sub-maximal response at any concentration.
A competitive antagonist binds reversibly to the same site and its block is surmountable by more agonist.
A non-competitive antagonist binds irreversibly; slope and maximum fall and the block cannot be overcome.
A mixed agonist–antagonist activates one receptor set while blocking another.
Selectivity is relative: most ligands act on several subtypes, which broadens use and creates off-target effects.

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Worked example

Reading a dose–response family of curves. An experiment produces five curves. Curve A and curve B reach the same maximum, but A lies to the left of B. Curve C reaches a lower maximum no matter how the concentration is raised. Curve D is curve A shifted to the right with the same maximum and the same slope. Curve E is curve A shifted to the right with a lower maximum and a flatter slope. You must identify the type of drug responsible for each curve.

Curves A and B share the same maximal response, so both drugs are full agonists. A reaches that maximum at a lower concentration, so A is the more potent of the two; potency is read from the horizontal position of the curve.
Curve C flattens below the maximum of A and B whatever the concentration. That is a partial agonist: its intrinsic activity is limited, so no dose can lift the response to the full agonist level.
Curve D keeps the same maximum and the same slope but needs more agonist to get there. A parallel shift to the right is the signature of a competitive antagonist, which binds reversibly and can be displaced — a surmountable block.
Curve E loses both slope and maximum. That is the signature of a non-competitive antagonist, which binds irreversibly, removes receptors from the available pool and cannot be overcome by raising the agonist concentration.
Add a mixed agonist–antagonist to the picture. Its curve would not be a single clean shape, because the drug activates one receptor population while blocking another, so the observed curve depends on how much of each type the tissue carries.

The shape of the curve is the fingerprint of the drug’s behaviour at the receptor: position on the horizontal axis tells you potency, height tells you efficacy, a pure right shift means surmountable blockade, and a loss of height or slope means an irreversible one.

Common misconception

Beginners often think that “antagonist” simply means “weaker agonist”, or that a competitive and a non-competitive antagonist differ only in strength. They differ in kind. A competitive antagonist can always be out-competed by enough agonist, while a non-competitive antagonist removes receptors from service, so no amount of agonist restores the response. That difference decides whether an overdose can be reversed.

Check your reasoning

A patient taking a full agonist becomes unwell, and you suspect too much receptor activation. In which case would giving more of the natural agonist make things worse, and in which case would you instead need an antagonist?

Reveal an answer

Giving more agonist makes things worse whenever the problem is that the receptors are already being activated too much; the answer there is an antagonist, and a competitive one if the block may need to be reversed later. More agonist is only useful when the problem is too little activation, for example because a partial agonist is occupying the receptors and preventing the full agonist from acting.

Where this comes from

BMS 123 General Pharmacology II lecture notes · Part Two, §3.3 Agonists and antagonists; §3.4.3 Dose–response curves for agonists and antagonists

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About this course and its sources

Bilingual lessons organised from the supplied BMS 123 General Pharmacology II lecture notes (Principles of Pharmacokinetics and Principles of Pharmacodynamics). Diagrams are original educational schematics; pharmacology, nursing and French-language review are pending.