4.13:
Drug-Receptor Interaction: Antagonist
An antagonist is a drug that strongly binds a receptor but does not activate it. Although it produces no effect by itself, it prevents the receptor from interacting with agonists or endogenous ligands, which blocks or reduces their effect.
Based on antagonist-receptor interaction, antagonists can be competitive or noncompetitive.
A competitive antagonist competes with an agonist to bind the receptor at the same site, stabilizing the receptor's inactive state. In a plot of agonist concentration versus response, an antagonist shifts the curve towards the right as it reduces the number of available receptors. Increasing antagonist concentration further reduces receptor availability, diminishing the effect of the agonist.
Such receptor-antagonist interactions are reversible. Increasing agonist concentration reverses the antagonist's effect by restoring agonist-receptor binding.
A noncompetitive antagonist binds covalently to the receptor's active site and prevents agonist binding. Even increasing the concentration of agonists cannot displace these antagonists from the receptor. Such irreversible antagonists lower the maximal effect of the agonist, reducing agonist efficacy.
4.13:
Drug-Receptor Interaction: Antagonist
An antagonist is a drug that binds strongly to a receptor without activating it. An antagonist prevents other molecules, such as neurotransmitters or hormones, from binding to the receptor and triggering a cellular response. Such interaction effectively hinders the normal physiological processes mediated by the receptor, resulting in various pharmacological effects depending on the specific receptor targeted.
Antagonists can be classified as competitive or noncompetitive based on their interaction with the receptor.
A competitive antagonist competes with an agonist to bind to the receptor at the same site. It reduces the number of available receptors and diminishes the effect of the agonist. Its effect is reversible, as increasing the agonist concentration restores the binding between the agonist and the receptor, counteracting the antagonist's actions. The effectiveness of a competitive antagonist can be overcome by increasing the concentration of the agonist. Examples of competitive antagonists include naloxone (used to reverse opioid overdose) and propranolol (used to block β-adrenergic receptors in the heart).
In contrast, noncompetitive antagonists bind covalently to the active site of the receptor. Even increasing the concentration of agonists cannot displace these irreversible antagonists from the receptor. As a result, noncompetitive antagonists lower the maximal effect of the agonist and reduce its efficacy. Examples of noncompetitive antagonists include phenoxybenzamine (used to block ɑ-adrenergic receptors) and ketamine (an NMDA receptor antagonist used for anesthesia).