Histamine H1 Receptor Antagonists

The histamine H1 receptor is a G protein-coupled receptor through which histamine mediates the contraction of smooth muscle and increases capillary permeability by contracting terminal venules; the same receptor also mediates neurotransmission in the central nervous system, where it regulates circadian rhythms, emotional and locomotor activities and cognitive functions. Drugs in this class compete with histamine for the receptor rather than activating it, so the smooth-muscle and capillary effects of a histamine response are blunted. Central occupancy is why the older members are sedating: the diphenhydramine label describes it as an antihistamine with anticholinergic (drying) and sedative side effects, and states that antihistamines appear to compete with histamine for cell receptor sites on effector cells.