Histamine Antagonists

HISTAMINE ANTAGONISTS

The effects of histamine released in the body can be reduced in several ways. Physiologic antagonists, especially epinephrine, have smooth muscle actions opposite to those of histamine, but they act at different receptors. This is important clinically because injection of epinephrine can be lifesaving in systemic anaphylaxis and in other conditions in which massive release of histamine— and other more important mediators—occurs.

Release inhibitors reduce the degranulation of mast cells thatresults from immunologic triggering by antigen-IgE interaction. Cromolyn and nedocromil appear to have this effect and have been used in the treatment of asthma, although the molecular mechanism underlying their action is not fully under-stood. Beta ₂-adrenoceptor agonists also appear capable of reducing histamine release.

Histamine receptor antagonists represent a third approach to the reduction of histamine-mediated responses. For over 60 years, compounds have been available that competitively antagonize many of the actions of histamine on smooth muscle. However, not until the H₂-receptor antagonist burimamide was described in 1972 was it possible to antagonize the gastric acid-stimulating activity of his-tamine. The development of selective H₂-receptor antagonists has led to more effective therapy for peptic disease . Selective H₃ and H₄ antagonists are not yet available for clinical use. However, potent and partially selective experimental H₃-receptor antagonists, thioperamide and clobenpropit, have been developed.