The effect of metiamide in in vitro and in vivo canine models of type I hypersensitivity reactions

Abstract

The histamine H2-receptor antagonist metiamide was evaluated in in vitro and in vivo canine models of immediate-type hypersensitivity reactions. At concentrations of 2 and 4 X 10(-4) M, the antagonist significantly increased the amount of histamine present in the medium surrounding passively sensitized canine lung fragments which had been challenged with ascaris antigen. In contrast, the compound was without effect on the release of a slow reacting substance of anaphylaxis. On the basis of these observations metiamide was investigated in an in vivo canine model of allergic asthma. At doses of 10, 30 and 50 mu moles/kg, the antagonist did not enhance the ascaris antigen-induced pulmonary pathophysiology. Similarly, at 10 and 50 mu moles/kg metiamide did not alter histamine-induced increases in pulmonary resistance or decreases in dynamic lung compliance. Insofar as the canine model of allergic asthma may be predictive of the human disease, it could be anticipated that the use of histamine H2-receptor antagonists may not be deleterious to allergic asthmatics.