Article date: November 1982
By: R.B. BARLOW, MARGARET CHAN in Volume 77, Issue 3, pages 559-563
Dose‐ratios obtained with pirenzepine on the guinea‐pig ileum at 30°C are indistinguishable from those obtained at 37°C.
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.
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.
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.
Dose‐ratios obtained with pirenzepine on the guinea‐pig ileum at 30°C are indistinguishable from those obtained at 37°C.
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.
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.
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.
DOI: 10.1111/j.1476-5381.1982.tb09331.x
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