THE EFFECTS OF pH ON THE AFFINITY OF PIRENZEPINE FOR MUSCARINIC RECEPTORS IN THE GUINEA‐PIG ILEUM AND RAT FUNDUS STRIP

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Abstract
1 Dose-ratios obtained with pirenzepine on the guinea-pig ileum at 30°C are indistinguishable from those obtained at 37°C. 2 In 0.1 m NaCl at 37°C the pKa of pirenzepine for the loss of its last ionizable proton is 8.2. The ionization of pirenzepine is therefore markedly affected by changes in pH in the physiological range. 3 In experiments with pirenzepine on guinea-pig ileum and rat fundus made over a range of pH, the dose-ratio increases with the proportion of the protonated form present. As expected, the slope of the graph of dose-ratio against proportion protonated depends on the concentration of antagonist. The changes in pH produce only small effects on dose-ratios obtained with pirenzepine monomethiodide. These effects of pH can account for some of the differences between estimates of the affinity of pirenzepine. 4 The logarithm of the affinity constant of the protonated form of pirenzepine for the receptors in guinea-pig ileum is estimated to be 6.93, compared with 6.94 for the receptors in rat fundus. However, for the non-protonated form the values appear to be below 5 for the ileum compared with about 6.4 for the rat fundus.