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

Abstract

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.