What is the Origin of Receptor Cross-Reactivity?

This concept is foundational to pharmacology, explaining the mechanism behind many drug side effects and the relative selectivity of compounds. It stems from the realization that few ligands possess absolute specificity, often possessing a binding affinity profile across a family of structurally related receptors.

What is the Mechanism of Receptor Cross-Reactivity?

The mechanism is rooted in molecular mimicry, where the chemical structure of the drug is sufficiently similar to an endogenous ligand to engage a secondary receptor, such as another subtype within the same family or an entirely different receptor system. For instance, certain steroid hormones or their synthetic analogues may cross-react with glucocorticoid or mineralocorticoid receptors in addition to their intended sex steroid receptors. This non-specific binding can trigger a cascade of unintended cellular responses, resulting in a side effect like fluid retention or altered glucose metabolism.

Receptor Cross-Reactivity

Meaning

Receptor Cross-Reactivity is a pharmacological phenomenon where a therapeutic ligand, such as a hormone or drug, binds to and activates or inhibits a receptor other than its intended or primary molecular target. This unintended interaction occurs due to structural similarities between the ligand and the non-target receptor’s natural substrate, leading to off-target effects and potential adverse clinical outcomes. It is a critical consideration in drug design and personalized medicine.