antihistamine

During an allergic reaction, cells release a flood of histamine that causes itching, sneezing, runny nose, and hives. An antihistamine sits on the receptors histamine would normally activate, like taking the seats in a theater so the messenger arrives but finds nowhere to deliver its message, so the allergy symptoms ease.

Most allergy antihistamines are antagonists (technically inverse agonists) at the histamine H1 receptor, a G-protein-coupled receptor. The classic pharmacophore is two aromatic rings attached to a short chain ending in a basic, protonatable nitrogen, a shape that mimics histamine well enough to occupy its binding site.

The class splits by generation. First-generation agents such as diphenhydramine are lipophilic, cross into the brain, and cause sedation; second-generation agents such as loratadine and cetirizine were designed to be more polar or to be kept out of the brain by transporters, so they relieve allergy with much less drowsiness. (A separate family, the H2 antagonists such as ranitidine, instead reduces stomach acid.)

An honest caveat: the sedation and dry-mouth of older antihistamines come from hitting other receptors (such as muscarinic acetylcholine receptors) off target, a reminder that 'an antihistamine' is rarely perfectly selective.