The effects of metiamide and H1 receptor blocking agents on anaphylactic response in guinea-pigs

Abstract

The effects of metiamide and of four H₁ receptor blocking agents (mepyramine, promethazine, clemastine and ketotifene) on anaphylactic reaction were studied in the guinea-pig. The H₁ blockers conferred partial protection which shows that with the experimental protocol utilized (challenge injection with high doses of antigen), histamine plays a lesser role than other mediators released or synthesized. Metiamide (30.0 mg/kg i.v.) noticeably enhanced the increase in pulmonary resistance observed during anaphylactic reaction and reduced the protective effect of the H₁ antagonists on this parameter and on histamine release. These effects might be explained by an inhibition — at least partial — of the negative feed-back mechanism through which histamine controls its own release, or by a specific action of metiamide in high doses. The transient tachycardia initially observed in anaphylactic shock is partly related to stimulation of cardiac H₂ receptors by the histamine released, since it is suppressed by metiamide.