Histamine receptors respond to the endogenous ligand histamine. The potency order of histamine at histamine receptor subtypes is H3 = H4 > H2 > H1.

Antagonists of all 4 histamine receptors have clinical uses: H1 antagonists for allergies (e.g. cetirizine), H2 antagonists for acid-reflux diseases (e.g. ranitidine), H3 antagonists for narcolepsy (e.g. pitolisant/WAKIX; Registered) and H4 antagonists for atopic dermatitis (e.g. ZPL-3893787; Phase IIa) and vestibular neuritis.