Histamine dihydrochloride

Routes of
administrationSubcutaneous injection, topicalATC codeLegal statusLegal status IdentifiersCAS NumberPubChem CIDChemSpiderUNIICompTox Dashboard (EPA)ECHA InfoCard100.000.272 Chemical and physical dataFormulaC₅H₁₁Cl₂N₃Molar mass184.06 g·mol⁻¹3D model (JSmol)

Histamine dihydrochloride (INN, 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).

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 such as Australian Dream and Golden Creme.^{[2] [3]}

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 AML, i.e. when patients have completed the initial chemotherapy. This combination has been reported to significantly reduce the risk of relapse in AML.^[4] The effect is particularly pronounced in patients in their first remission who are below the age of 60.^[5]

The combination of histamine dihydrochloride and interleukin-2 was approved for use in AML patients within the European Union in October 2008^[6] and will be 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.^[7] 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.

References