Pharmacodynamics: receptors and signaling

Reading time: ~2 min · Part of the free certification in peptide science

Pharmacodynamics describes the drug's action on the body. In peptides, almost all activity arises from binding to a receptor with a site complementary to the molecule.

Many peptide receptors are G protein-coupled receptors (GPCR). When activated, the G protein mobilizes second messengers —cyclic AMP (cAMP) via adenylate cyclase, or calcium/IP₃ via phospholipase C— that amplify the signal and start cellular responses. Other peptides act on receptors with tyrosine kinase activity (e.g., the insulin/IGF-1 pathway).

Parameters that define the interaction

• Affinity: binding strength, inversely related to the dissociation constant K_d. Lower K_d, higher affinity.
• Potency: expressed as EC₅₀ (concentration producing 50% of the maximum effect). Lower EC₅₀, higher potency.
• Efficacy: maximum achievable response once bound.
• Selectivity: preference for the target over related receptors; it determines the margin between the desired effect and off-target effects.

Spectrum of activity and biased agonism

An agonist activates the receptor; an antagonist blocks it without activating it; a partial agonist produces a submaximal response. An advanced concept is biased agonism: a ligand can preferentially activate one signaling pathway (e.g., G protein) over another (β-arrestin) from the same receptor, which allows therapeutic effects to be separated from adverse ones. Dual and triple agonists (Module 3) take this logic to the extreme: a single molecule designed to activate two or three different receptors in a balanced way.

Educational content for scientific purposes. It distinguishes preclinical from clinical evidence and is not medical advice, diagnosis or a recommendation for use. NeoPeptidos products are sold labelled for research use only (RUO).