FFP1 - Antagonists (1)

1. Antagonists

  • Definition:

    • Antagonists are substances that bind to a receptor but do not provoke a biological response.

    • They prevent agonists (ligands that activate receptors) from binding and eliciting a response.

Intrinsic Activity (α)

α = 1: Full Agonist

1 > α > 0: Partial Agonist

α = 0: Antagonist

Competitive Antagonists

  • Binding Site:

    • Competes with the agonist for the same binding site on the receptor.

    • Reversible binding, allowing agonist to displace it.

    • Excess agonist can overcome its effect.

    • Maximum effect of agonist is unchanged.

    • Requires higher agonist dose to reach maximum effect.

    • (shifts graph to the right)

    • Effective concentration 50 (EC50) increases

Non-Competitive Antagonists

  • Binding Site: Binds to a different site than the agonist.

  • Reversible binding

  • Also known as an allosteric antagonist or inhibitor.

  • Cannot be overcome by increasing agonist concentration.

  • Effect on Maximal Response

  • (shifts graft downwards)

  • EC50 is unchanged

2. Types of Antagonists

2.1 Reversible Antagonists

  • Definition:

    • Binding is reversible, meaning the antagonist can be removed or displaced by a higher concentration of the agonist.

  • Effect on Dose-Response Curve:

    • Increases the dose of agonist required to achieve maximum effect (Emax).

    • Log dose-response curve shifts to the right, indicating that higher concentrations of agonist are needed.

2.2 Irreversible Antagonists

  • Definition:

    • Bind to receptor, permanently inactivating it.

    • Cannot be displaced by other ligands.

  • Effect on Dose-Response Curve:

    • Maximum effect (Emax) of the agonist is reduced.

    • Log dose-response curve shifts down, reflecting the reduced number of available receptors

4. Comparing Potency

  • ED50:

    • Effective dose that elicits a therapeutic effect in 50% of the population tested.

  • IC50:

    • Inhibitory concentration that reduces the response of an agonist by 50%.

    • Determined by adding increasing doses of antagonist and observing the response.

5. Desensitization and Tolerance

  • Desensitisation/Tachyphylaxis:

    • the effect of a drug diminishes when it is given repeatedly or continuously.

  • Tolerance:

    • Similar to desensitisation but develops more slowly

  • Refractoriness:

    • A state where the effect diminishes due to factors like receptor changes or physiological adaptation.

6. All-or-None Responses

  • Graded Dose-Response curve:

    • Continuous scale responses (e.g., heart rate).

  • Quantal Response:

    • All-or-none effect (e.g., presence or absence of a medical condition).