Metiamide—An orally active histamine H₂-receptor antagonist

Abstract

Metiamide has been found to be about 10 times more active than burimamide in vitro in antagonizing histamine H₂-receptors and nearly 5 times more active in vivo as an antagonist of histamine or pentagastrin-stimulated secretion. Effective oral ED₅₀ doses for inhibition have been estimated as 25 μmole kg⁻¹ against basal secretion in rats and 16 μmole kg⁻¹ against maximal histamine-stimulated secretion in dogs. Administration of metiamide orally daily for 90 days with doses of 1,500 μmole kg⁻¹ to rats and 700 μmole kg⁻¹ to dogs produced signs of kidney damage as the dominant lesion in both species. These toxic doses are roughly 60 and 44 times greater than the ED₅₀ doses in the rat and dog, respectively. These results show that metiamide has the degree of activity and safety needed for a compound to be a candidate for thorough clinical evaluation.