Information about Receptor Antagonist

A receptor antagonist is a drug that does not provoke a biological response itself upon binding to a receptor, but blocks or attenuates agonist-mediated responses. It may be competitive (or surmountable), i.e. it binds reversibly to a region of the receptor in common with an agonist, but occupies the site without activating the effector mechanism. The effects of a competitive antagonist may be overcome by increasing the concentration of agonist, thereby shifting the equilibrium and increasing the proportion of receptors which the agonist occupies. Alternatively, antagonists may be unsurmountable, where no amount of agonist can completely overcome the inhibition once it has been established. Unsurmountable antagonists may bind covalently to the agonist binding site (competitive irreversible antagonists), in which case there is a period before the covalent bond forms during which competing ligands can prevent the inhibition. Other types of unsurmountable antagonists act allosterically at a different site on the receptor or an associated ion channel.^[1]

In pharmacology an antagonist is a binding partner (ligand) of a receptor by disrupting the interaction and inhibiting the function of an agonist or inverse agonist at their receptors. Antagonists are said to have affinity but no efficacy for their cognate receptors.

Most drugs exert effects, both beneficial and detrimental, by interacting with specific receptors that are present on or within cells. Historically, receptors were thought to act much like light switches. Agonists were thought to turn "on" a single cellular response by binding to the receptor, thus initiating a biochemical mechanism for change within a cell. Antagonists were thought to turn "off" that response by 'blocking' the receptor from the agonist.

Activity (IC50)

The potency of an antagonist is usually defined by its IC₅₀ value. This can be calculated for a given antagonist by determining the concentration of antagonist needed to elicit half inhibition of the maximum biological response of an agonist. Elucidating an IC₅₀ value is useful for comparing the potency of drugs with similar efficacies. The lower the IC₅₀, the greater the potency of the antagonist the lower the concentration of drug that is required to inhibit the maximum biological response.

Types

Today's current theories involving receptor antagonists center around an antagonist's ability to counteract the effects of agonists and inverse agonists (if one exists for the specific receptor). Antagonists work by binding to receptors preventing them from eliciting a biologial response. On their own, "silent" antagonists do not exert a biological effect (no efficacy).

There are three kinds of receptor antagonists:

• Competitive antagonists reversibly bind to receptors and compete with other agonists and antagonists for a specific binding site (They displace agonists or inverse agonists). An example is the interleukin-1 receptor antagonist, IL-1Ra. High concentrations of a competitive agonist will displace the antagonist from the receptor.
• Reversible non-competitive antagonists bind to a different binding-site from the agonists, exerting their action to that receptor via the other binding site. They are called non-competitive antagonists because they do not compete for the same binding site as the agonists.
• Irreversible antagonists bind covalently to the receptor binding site. They do not compete with agonists since due to the covalent nature of the bond they can not be displaced from the receptor by raising the concentration of an agonist.

Antagonists may be naturally occurring as is the case with physiological antagonists, or they may be synthetic and made to mimic the body's physiological antagonists.

Recently, the discovery of inverse agonists and other concepts such as functional selectivity have broadened traditional definitions. Functional selectivity means that a ligand can concurrently behave as an agonist and antagonist at the same receptor, depending upon the effector system.

A further important characteristic is affinity − the tendency to bind to a receptor.

See also

• Agonist
• Enzyme inhibitor
• Inverse agonist
• Efficacy
• Affinity

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