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Agonist:

An agonist is a compound that binds to a receptor to produce the same response as an endogenous ligand. A full agonist is capable of producing the maximal response, greater than that of the endogenous ligand, while binding to a smaller number of receptors. This occurs due to the total conformational change of the receptor upon compound binding and allows for maximum activation of the receptor. Conversely, a partial agonist will produce less of a conformational change, which results in less activation and a lower efficacy. Even if a partial agonist were to bind to more receptors than needed to elicit a response, the efficacy and activation of the receptor would not change. The increased binding also prevents other agonists from acting on the receptors, therefore creating a sub-maximal response. An inverse agonist is a compound that binds to the receptor site and produces the opposite effect of the agonist. In addition to this, an inverse agonist also prevents binding of the receptor sites to any other ligand, which decreases the efficacy even further.

  • Full: Maximal Efficacy
  • Partial: Sub-maximal Efficacy
  • Inverse: Produces opposite biological effects as the full
    agonists

Antagonist:

An antagonist is a compound that binds to a receptor but does not elicit any biological response. This type of compound can be structurally similar to an agonist for the receptor, however its binding results in no activation and therefore has zero efficacy. Competitive antagonists are compounds that mimic agonists and bind directly to the active site on the receptor in order to block the action that the agonist would elicit. Competitive antagonists are reversible, meaning that they that bind non-covalently to the same receptor that the agonist would and can disassociate quite easily. This creates a situation where an increase in agonist dose will be able to overcome the limiting effects of the antagonist. Non-competitive antagonists differ in that they bind to an allosteric site of the receptor so that the active site cannot be bound by any other compound. This non-competitive binding is not able to be overcome by increasing the dose of agonist present. Since the binding sites of the agonist and antagonist in this case are different, the agonist is unable to displace the antagonist on the receptor and the effect is irreversible. Irreversible antagonists form stable, covalent bonds with the receptors and the binding is permanent. This effectively destroys the receptor and cannot be overcome by washing or increasing ligand dose.

  • Reversible & Competitive: Transiently bound to the same site as
    Agonists
  • Non-competitive: Bound to a different site as Agonists
  • Irreversible: Covalently bind to the same site as Agonists

Agonist/Antagonists

Mixed agonists/antagonists also exist and can have varying responses based on the conditions present. The type of response that occurs is often dependent on the receptor site that the compound is binding to. These compounds can act as an agonist for one receptor and also as an antagonist for another. They are often compounds that interact with various opioid receptors.