Radioligand

A radioligand is a molecule that binds to a specific biological target — typically a receptor, transporter, or enzyme — and carries a radioactive label so researchers can detect and quantify that binding with precision. The combination of chemical specificity and radioactive detectability makes radioligands the standard tool for characterising how tightly and selectively a drug attaches to its molecular targets.

The affinity and selectivity values found on substance pharmacology pages — Ki figures, pKi tables, binding profiles — originate almost entirely from radioligand binding studies conducted in the laboratory.

How it works · its role

In a binding assay, a radioligand is mixed with a preparation containing the target of interest — often membrane fragments from brain tissue, or a purified receptor expressed in cell lines. The radioligand competes to occupy the receptor's binding site. After equilibrium is reached, bound and unbound ligand are separated (usually by filtration) and the retained radioactivity is measured.

Saturation binding floods the receptor with increasing concentrations of the radioligand to determine how tightly it binds (the dissociation constant, Kd) and how many binding sites are present (Bmax). This establishes the basic parameters of the receptor–ligand relationship.

Competition binding, more commonly used in drug research, tests how effectively an unlabeled compound displaces the radioligand — yielding an inhibition constant (Ki) that describes the unlabeled drug's own affinity at that target. These Ki values are the figures cited in binding profiles throughout this encyclopedia.

The isotopes most commonly used are tritium (³H) and iodine-125 (¹²⁵I), chosen for their sensitivity and manageable half-lives. In positron emission tomography (PET), radioligands labeled with carbon-11 or fluorine-18 can be administered to living subjects, allowing receptor occupancy to be imaged in the brain directly.

Relevance to substances & effects

Every receptor affinity value cited on a substance page traces back to a radioligand study. When a profile states that a compound has high affinity at the μ-opioid, or that a classic psychedelic binds tightly at 5-HT₂A, those numbers were measured in a competition binding assay using a radioligand reference compound.

Selectivity profiles — whether a drug hits one receptor cleanly or spreads across several — are determined the same way. Two substances in the same class may have meaningfully different binding constants across receptor subtypes, helping explain why their subjective effects diverge despite superficial chemical similarity.

Transporter affinity assays use the same principle to measure how strongly a drug blocks the serotonin, dopamine, or norepinephrine reuptake transporters. These figures feed directly into interaction risk predictions — radioligand data is the foundation on which the encyclopedia's binding and interaction layer is built.