Moleculium

CID 774

C5H9N3

Histamine

  • C 5
  • H 9
  • N 3
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17 atoms, 17 bonds.
Ball-and-stick model of histamine: 5 carbon atoms, 9 hydrogen atoms and 3 nitrogen atoms, 17 bonds (15 single, 2 double). Carbon is grey, hydrogen white, nitrogen blue.
IUPAC name
2-(1H-imidazol-5-yl)ethanamine
Molar mass
111.148(15) g/mol
Atoms
17
SMILES
C1=C(NC=N1)CCN
InChIKey
NTYJJOPFIAHURM-UHFFFAOYSA-N
PubChem CID
774

Made of

C , Carbon, nonmetal H , Hydrogen, nonmetal N , Nitrogen, nonmetal
Structural formula of histamine. Each unlabelled corner is a carbon atom, and the six hydrogens on carbon are not drawn. It shows which atoms are joined to which, not the shape. The model above shows the shape. Structural formula of histamine, drawn flat from PubChem's 2D record: 5 carbon atoms, 9 hydrogen atoms and 3 nitrogen atoms, 17 bonds (15 single, 2 double). Each unlabelled corner is a carbon atom, and the six hydrogens on carbon are not drawn. Symbols carry their usual colours: nitrogen blue. A structural formula shows how the atoms are joined, not the shape of the molecule.

The sneezing, runny nose and itchy, watering eyes of a seasonal allergy are the work of one small molecule, which also tells the stomach to make acid. Histamine is a signalling molecule: it carries messages from one cell to another. Five carbon, nine hydrogen and three nitrogen atoms give the formula C5H9N3 and a molar mass of 111.15 g/mol. PubChem’s IUPAC name for it is 2-(1H-imidazol-5-yl)ethanamine, and ChEBI, the Chemical Entities of Biological Interest database, classes it among the imidazoles, its ring being 1H-imidazole.

The Hazardous Substances Data Bank (HSDB) describes needles, crystallised from chloroform, that melt at 83 to 84 °C. The solid is deliquescent, taking up moisture from the air until it dissolves, and it dissolves freely in water, alcohol and hot chloroform. Its medicinal forms are two salts, histamine phosphate and histamine dihydrochloride. The US National Cancer Institute (NCI) lists its use in tests for asthma, allergies and stomach acid secretion.

Structure and bonding

Five atoms close histamine’s ring, three carbons and two nitrogens, and the nitrogens differ as PubChem draws them: one carries a hydrogen, the other none. A chain of two CH2 groups runs from the ring carbon beside the N–H nitrogen out to an NH2 group. With Labels on, three N symbols stand out among the 17 atoms, two in the ring and one ending the chain.

Ball-and-stick shows the two double bonds PubChem draws, both in the ring: a C=N at the hydrogen-free nitrogen and a C=C between two carbons. They alternate with single bonds, the pattern Chem1 calls a conjugated system (benzene shows what follows). The ring and its N–H hydrogen lie in one plane in PubChem’s computed model. Space-filling makes that ring a small flat disc, with the extended chain as its tail.

The model is the uncharged molecule, without formal charges. An NH2 group bonded to carbon marks an amine, and Chem1 ranks amines as the commonest organic bases, giving weakly alkaline solutions in water. ChEBI names the form that has gained a proton histaminium, which the viewer does not draw.

Where it turns up

The body makes histamine from histidine: the enzyme histidine decarboxylase splits off carbon dioxide and leaves the amine. It is held in the granules of mast cells and basophils, two kinds of immune cell. The NCI finds mast cells in connective tissue throughout the body, especially beneath the skin and in the lungs and intestines.

In the brain it serves as a neurotransmitter (serotonin explains the term). Enterochromaffin-like cells in the glands of the stomach lining produce it too. They release it in response to gastrin, and it prompts the parietal cells to release hydrochloric acid.

In humans two main routes clear it, HSDB records: histamine N-methyltransferase, which adds a methyl group to the ring, and diamine oxidase. Their products have little or no activity and leave in the urine.

Bacteria form it in decomposing fish such as mackerel, tuna, sardines and anchovies. The US Food and Drug Administration (FDA) notes that it may also form in cheese and sauerkraut.

Why it matters

Allergy symptoms begin with a release of histamine. Mast cells and basophils pick up IgE, a molecule made by B cells, and when an antigen, the offending substance, links those IgE molecules the cells empty their granules. Small blood vessels widen and turn leaky, which lets white blood cells and other protective substances through and can make the tissue swell. In an allergy the immune system has overreacted to something harmless. More than 8 per cent of US adults had hay fever in 2015, MedlinePlus reports.

The severe form is anaphylaxis, which can be fatal: airways may swell until breathing stops, and blood pressure can drop fast enough to starve organs of blood. It is treated with epinephrine. Drugs that block histamine’s action are called antihistamines.

Fish in which histamine has formed causes scombrotoxin poisoning, also called histamine poisoning, with symptoms that often look like an allergic reaction. From 1990 to 2007, 379 outbreaks involving 1,726 people were reported in the United States, FDA notes, with the real number believed far higher and no deaths confirmed.

Properties

Properties of histamine Molar mass summed from IUPAC/CIAAW 2024 standard atomic weights; formula, atom and bond counts and PubChem's molecular weight from PubChem CID 774.
Property Value Unit Source
Molecular formula (Hill order) C5H9N3
Molar mass 111.148(15)   g/mol g/mol IUPAC/CIAAW 2024
Carbon atoms 5
Hydrogen atoms 9
Nitrogen atoms 3
Bonds 17
Single bonds 15
Double bonds 2
PubChem molecular weight 111.15   g/mol g/mol PubChem

Safety

As a pure chemical, histamine may cause allergy or asthma symptoms if inhaled and may cause an allergic skin reaction. Both statements belong to its classification under the Globally Harmonized System (GHS), which carries the signal word Danger. It adds that histamine is toxic if swallowed, irritates the skin, seriously irritates the eyes and may irritate the airways. Each statement appears in 93.3% of the reports sent to the European Chemicals Agency. The PubChem Laboratory Chemical Safety Summary for histamine sets them out in full.

Questions

What does histamine do in the body?

Histamine strongly stimulates stomach secretion, tightens the smooth muscle of the airways, widens blood vessels and serves as a neurotransmitter, on the account of Medical Subject Headings (MeSH). It also helps the brain stay awake, MedlinePlus notes, and raises the heart rate, according to the US National Cancer Institute. The tightening of airways and gut runs through H1 receptors, the sites on cells that histamine binds to, and stomach secretion through H2 receptors.

What does a histamine molecule look like?

PubChem's model has 17 atoms: five carbons, three nitrogens and nine hydrogens. Three carbons and two nitrogens form a five-membered ring, flat in the computed model, with a hydrogen on one of its nitrogens. A two-carbon chain ending in an NH2 group extends from one ring carbon. Histamine has no single central atom of the kind Chem1 names shapes around, only several centres: the ring, two chain carbons and the NH2 nitrogen.

What do antihistamines do?

They block the action of histamine by keeping cells from detecting it. The name follows from histamine being one of the chemicals the immune system releases in an allergy. The classical antihistamines block H1 receptors only, the Hazardous Substances Data Bank records. A second class binds H2 receptors without activating them and is used to treat ulcers by holding back acid secretion. Some antihistamines bring on sleepiness, and others are used against acid reflux.

Why does spoiled fish contain histamine?

Bacteria living on the fish make decarboxylase enzymes, which turn its natural histidine into histamine as the fish decomposes, says the US Food and Drug Administration (FDA). The US Centers for Disease Control and Prevention traces the resulting illness to fish not properly chilled after the catch. Such fish may look and smell normal, and neither cooking, canning nor freezing lessens the toxic effect. FDA describes the toxin, scombrotoxin, as a mixture in which histamine is prominent.

Made of the same elements

Sources

  1. PubChem CID 774, histamine
  2. IUPAC/CIAAW, Abridged Standard Atomic Weights 2024
  3. PubChem Laboratory Chemical Safety Summary for histamine (CID 774)
  4. Stephen Lower, Chem1 General Chemistry, §10.6 Types of Acids and Bases (LibreTexts, CC BY 3.0)
  5. Stephen Lower, Chem1 General Chemistry, §9.7 The Hybrid Orbital Model II (LibreTexts, CC BY 3.0)
  6. Stephen Lower, Chem1 General Chemistry, §9.5 Molecular Geometry (LibreTexts, CC BY 3.0)
  7. National Cancer Institute, NCI Dictionary of Cancer Terms: histamine
  8. National Cancer Institute, NCI Dictionary of Cancer Terms: mast cell
  9. National Cancer Institute, NCI Dictionary of Cancer Terms: antihistamine
  10. MedlinePlus (National Library of Medicine), Histamine: The Stuff Allergies are Made of
  11. US Food and Drug Administration, Know Which Medication Is Right for Your Seasonal Allergies (2024)
  12. NLM Medical Subject Headings (MeSH), Histidine Decarboxylase
  13. NLM Medical Subject Headings (MeSH), Histamine Release
  14. NLM Medical Subject Headings (MeSH), Enterochromaffin-like Cells
  15. NLM Medical Subject Headings (MeSH), Histamine H2 Antagonists
  16. US Food and Drug Administration, Bad Bug Book, Second Edition (2012): Scombrotoxin
  17. CDC, Travelers' Health: Food Poisoning from Seafood