What is an indirect antagonist?

An indirect antagonist is a type of drug that typically works by attaching to a binding site on a receptor that is different from the principal ligand’s binding site. This can lead to a decrease in the receptor's activity without directly blocking the binding of the principal ligand. By binding elsewhere, the indirect antagonist can alter the receptor's conformation or its ability to respond to the principal ligand, effectively reducing its effect.

This is distinct from direct antagonists, which compete directly with the principal ligand for binding and thus block its action more straightforwardly. An indirect antagonist can modify the receptor's behavior indirectly, which can lead to decreased agonist efficacy even when the agonist is still capable of binding. Understanding this mechanism is essential in pharmacology and neurobiology, especially in the context of drug interactions and therapeutic applications.