METIAMIDE - AN ORALLY-ACTIVE HISTAMINE H-2-RECEPTOR ANTAGONIST

Metiamide has been found to be about 10 times more active than burimam ide in vitro in antagonizing histamine H-2-receptors and nearly 5 time s more active in vivo as an antagonist of histamine or pentagastrin-st imulated secretion. Effective oral ED(50) doses for inhibition have be en estimated as 25 mu mole kg(-1) against basal secretion in rats and 16 mu mole kg(-1) against maximal histamine-stimulated secretion in do gs. Administration of metiamide orally daily for 90 days with doses of 1,500 mu mole kg(-1) to rats and 700 mu mole kg(-1) to dogs produced signs of kidney damage as the dominant lesion in both species. These t oxic doses are roughly 60 and 44 times greater than the ED(50) doses i n the rat and dog, respectively. These results show that metiamide has the degree of activity and safety needed for a compound to be a candi date for thorough clinical evaluation.