Discovery and identity
Histamine is a small molecule made from the amino acid histidine. It was first synthesized in 1907, and in 1910 Britain's Henry Dale and Patrick Laidlaw showed it constricts airways and drops blood pressure, mimicking anaphylaxis. In the body it is stored in granules inside mast cells in the skin, airways and gut lining; when an allergen such as pollen binds IgE antibodies on these cells, histamine floods out. This is the starting point of a type I hypersensitivity reaction.
Four receptors, many symptoms
What histamine does depends on which receptor it hits. H1 activation makes blood vessels widen and leak, causing a runny nose, sneezing, swelling and itch, showing up as hives on the skin, allergic rhinitis in the nose and narrowing in the airways. H2 receptors increase acid secretion by stomach cells. Histamine neurons in the brain use H1 and H3 receptors to keep us awake, and H4 helps steer immune cells. So histamine is both an allergy mediator and a signal for alertness and digestion.
Antihistamines and histamine intolerance
Daniel Bovet found the first antihistamine compound in 1937 and won the 1957 Nobel Prize; in 1972 James Black's team defined the H2 receptor and developed acid blockers such as cimetidine. First-generation H1 blockers like diphenhydramine enter the brain and block wakefulness, which is why they cause drowsiness and appear in sleep aids, while second-generation drugs such as cetirizine and fexofenadine are far less sedating. H2 blockers have been used for GERD and ulcers. "Histamine intolerance," with headaches or flushing after aged cheese, wine or oily fish, may involve low levels of the enzyme DAO, but agreed diagnostic criteria do not yet exist.
This article is general health information and is not a substitute for diagnosis or treatment. If symptoms persist, see a doctor.
FAQ
- Why do some antihistamines make you sleepy?
- Brain histamine is a wake-promoting signal, and first-generation antihistamines cross into the brain and block it. Ask a pharmacist about a non-drowsy second-generation option before driving.
- I got hives after eating mackerel. Is it an allergy?
- It may be a fish allergy, but it can also be scombroid poisoning from histamine that builds up in poorly stored oily fish. If it recurs, see a doctor to find the cause.
Sources reviewed: 2026-10-26
References
- Dale, H. H., & Laidlaw, P. P. (1910). The physiological action of β-iminazolylethylamine. The Journal of Physiology, 41(5), 318–344.
- Black, J. W., Duncan, W. A., Durant, C. J., Ganellin, C. R., & Parsons, E. M. (1972). Definition and antagonism of histamine H2-receptors. Nature, 236, 385–390.
- Simons, F. E. R., & Simons, K. J. (2011). Histamine and H1-antihistamines: celebrating a century of progress. Journal of Allergy and Clinical Immunology, 128(6), 1139–1150.