Nutrient solution may alter the effect of the H2 blocker famotidine in the guinea pig papillary muscle.

The effect of different nutrient fluids (Ringer or Krebs) on the antagonism induced by the new H2 blocker famotidine against histamine was studied in the guinea pig isolated papillary muscle. The response to histamine was the same in Ringer and in Krebs solutions, as for threshold concentration and maximum response, conversely the antagonism induced by famotidine was found to be dependent on the nutrient fluid employed. It was competitive for low concentrations of the drug in both fluids, whereas the unsurmountable antagonism caused by higher concentrations in Ringer was reversed into a classical competitive one in Krebs. The potency of famotidine did not vary (pA2 values = 7.86 and 8.09 in Ringer and Krebs, respectively). The addition of PO4 or Mg++ to Ringer or the pH adjustment, in order to minimize the differences in the ionic content, did not modify the results obtained. The above data suggest that the antagonism by high concentrations of famotidine against histamine may be competitive or unsurmountable according to the nutrient fluid employed and stressed the importance of the ionic environment in the drug-receptor interaction.