Part III The action in the rat

administered orally in a small pellet of bread 60 to 90 minutes before commencing the histamine infusion (2.0 mg/hr). In three experiments, 200 mg SC 15396 was given intragastrically via the gastric cannula 60 minutes before the infusion. Significant depression of secretion over control experiments was not demonstrable by either technique. In several of the test experiments, however, particulate SC 15396 was recovered in moderate quantity from the gastric collections; thus one could not be certain how much SC 15396 was being absorbed. It was therefore decided to assess the effect of a large intravenous dose of SC 15396 on established histamine secretion in a gastric fistula dog. In four experiments on one gastric fistula dog 100 mg SC 15396 (5.5 mg/kg) was used. Although some inhibition appeared to occur, this was not statistically significant. When the dose was raised to 200 mg (11 mg/kg), however, prompt and highly significant inhibition of secretion (Fig. 16) resulted (p < 0.001 for 30-minute periods up to two hours after SC 15396). No toxic effects were noted even with this large intravenous dose.