Histamine dihydrochloride

Histamine dihydrochloride (trade name Ceplene) is a salt of histamine that is used as a drug for the prevention of relapse in patients diagnosed with acute myeloid leukemia (AML).

Histamine dihydrochloride

Clinical data
Trade names	Ceplene
License data	EU EMA: by INN
Routes of administration	Subcutaneous injection, topical
ATC code	L03AX14 (WHO)
Legal status
Legal status	Approved for use in the EU (2008) and Israel (2011)
Identifiers
IUPAC name 2-(1H-imidazol-5-yl)ethanamine dihydrochloride
CAS Number	56-92-8
PubChem CID	11309913
ChemSpider	5613
UNII	3POA0Q644U
CompTox Dashboard (EPA)	DTXSID1058767
ECHA InfoCard	100.000.272
Chemical and physical data
Formula	C5H11Cl2N3
Molar mass	184.06 g·mol−1
3D model (JSmol)	Interactive image
SMILES C1=C(NC=N1)CCN.Cl.Cl
InChI InChI=1S/C5H9N3.2ClH/c6-2-1-5-3-7-4-8-5;;/h3-4H,1-2,6H2,(H,7,8);2*1H Key:PPZMYIBUHIPZOS-UHFFFAOYSA-N

It is also an FDA-approved^[1] active ingredient for topical analgesic use for the temporary relief of minor aches and pains of muscles and joints associated with arthritis, simple backache, bruises, sprains, and strains and is available in over-the-counter (OTC) products.^{[medical citation needed]}

Use in leukemia

Histamine dihydrochloride is administered in conjunction with low doses of the immune-activating cytokine interleukin-2 (IL-2) in the post-remission phase of acute myeloid leukemia (AML), i.e. when patients have completed the initial chemotherapy. This combination has been reported to significantly reduce the risk of relapse in AML.^[2] The effect is particularly pronounced in patients in their first remission who are below the age of 60.^[3]

The combination of histamine dihydrochloride and interleukin-2 was approved for use in AML patients within the European Union in October 2008^[4] and is marketed in the EU by the Swedish pharmaceutical company Meda. The drug is also available through a named patient program in several other countries (excluding the US).

Proposed mechanism of action

Histamine dihydrochloride acts by improving the immune-enhancing properties of IL-2, and laboratory studies have shown that this combination can induce immune-mediated killing of leukemic cells.^[5] The treatment (in the form of subcutaneous injections) is given in 3-week cycles by the patients at home for 18 months, thus coinciding with the period of highest relapse risk. The side-effects include transient flush and headache, whereas IL-2 may induce low-grade fever and inflammation at the site of injection. Histamine dihydrochloride has been developed by researchers at the University of Gothenburg, Sweden.