Reversible versus irreversible binding

Reversible versus irreversible binding

 Ligand binding can be classified into two types:

  • reversible - a chemical bond is formed which easily dissociates again.
  • irreversible - a chemical bond is formed in which the product is thermodynamically much more stable than the reactants such the reverse reaction does not take place (normally: ‘covalent binding’).

Agonists, which activate the receptor, are almost always reversible ligands.


Irreversible ligands always block receptor action, and are commonly referred to as non-competitive antagonists (although (ir)reversibility and (non-)competitivity are two different terminologies!). Once an irreversible ligand has bound the receptor, the receptor will not be available for other ligands anymore.

The difference between reversible and irreversible binding has practical consequences. For example with aspirin, which causes irreversible inhibition of platelet COX-1. The duration of effect of aspirin as an anti-platelet drug is therefore not related to the half-life of aspirin, but to the turn-over rate (‘half-life’) of the platelet.