Histamine Release by Basic Compounds

  • Adolfo M. Rothschild
Part of the Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology book series (HEP, volume 18 / 1)


The demonstration that histamine, a normal constituent of animal tissues could be released in its pharmacologically active form in animals submitted to peptone or anaphylactic shock, led to extensive studies of other conditions in which this release could occur. The first demonstration of a direct histamine releasing action of a drug possessing basic groups in its molecule, was given by Alam and et al. (1939), who showed that curarine could release considerable amounts of histamine from dog muscle in vivo. Subsequent work by different groups of investigators showed that a great number of basic organic compounds, some having quite simple chemical structures, could provoke the release of histamine from non-sensitized tissues (Schild and Gregory, 1947; MacIntosh and Paton, 1949; Rocha e Silva and Schild, 1949, etc.). An important early outcome of these studies was the differentiation of this action from drug allergy, a condition which is also characterized by the release of histamine following exposure to certain organic compounds; however, in contrast to the basic histamine releasers, these act only on sensitized tissues. As shown in Table 1, the list of basic histamine releasers includes now over one hundred compounds, some only active in the experimental animal but others possessing considerable activity in the human subject, where they can give rise to “histaminic” symptoms such as flushing, tachycardia, itching, edema, gastrointestinal distress and bronchospasm. Several drugs of clinical importance, including curarizing agents, opium alkaloids, atropine, quinine, antibiotics, chloroquine and trypanocidal amidines have been shown to be potentially able to elicit these reactions (Lewis, 1927; Kirk and Henry, 1944; West, 1938; Grob and et al. 1947; Salter and White, 1949). Effective preventive or curative measures for the control of these side effects are available, and have been reviewed along with the discussion of proper skin tests to foretell histamine release in the human subject (Collier, 1956; Collier and MacAuley, 1952; Paton, 1959).


Mast Cell Histamine Release Basic Compound Mast Cell Granule Histamine Liberation 
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© Springer-Verlag Berlin Heidelberg 1966

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  • Adolfo M. Rothschild

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