Toxicity of Histamine and Antagonism between Histamine and Antihistamines in Various Strains of Mice

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Abstract
Sensitivity of 4 strains of mice to histamine was compared. Within one strain older and heavier mice are more resistant. The more resistant a strain or weight range of mice to histamine, the less protection is afforded by antihistamines. This is not due to higher antihistamine requirement to antagonize the higher lethal doses of histamine, since actually higher dose levels of antihistamines synergize with the toxicity of histamine in the highly histamine resistant strains of mice; antihistamine doses which protect other strains, increase the toxic ity of histamine. On the basis of these and pertinent data from the literature it is suggested that the toxicity of histamine is manifested through 2 different mechanisms; of which only one is antagonized by antihistamines. In various spp. and strains, one or the other mechanism may predominate.