The influence of an antihistamine drug on the release of histamine in the unanaesthetized dog / by W.D.M. Paton and M. Schachter.

  • William Paton
Date:
[1951?]
Catalogue details

Licence: In copyright

Credit: The influence of an antihistamine drug on the release of histamine in the unanaesthetized dog / by W.D.M. Paton and M. Schachter. Source: Wellcome Collection.

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    the gastric secretion resulting from Compound 48 / 80 did not become maximal until the facial oedema began to decline. Propamidine was tested in the same way, and it also produced gastric secre¬ tion, facial oedema (cf. Lourie and York, 1939), and itching ; as with Compound 48/80, a vigorous gastric secretion was obtained in the presence of mepyramine. Similarly, gastric secretion in an anaesthetized animal following continuous infusion of propamidine was not significantly altered by mepyramine in the same dose. Propamidine, however, proved unsatisfactory for the purpose of this investigation, because after receiving several injections the animals gradually became moribund and had to be sacrificed. This drug was therefore used in only a few experiments. Development of refractoriness to compound 48/80 With repeated injections of Compound 48/80, given at intervals of 2-7 days, the gastric secretory response progressively diminished in all animals (Table I). This decreasing effectiveness of Compound 48/80 was not due to a fall in sensitivity of the gastric glands to histamine, since histamine injected subcutaneously still elicited the usual secretion. A condition of complete refractoriness to Compound 48/80 was obtained by decreasing the interval between injections (Fig. 2). Such an animal not only shows no gastric secretory response to Compound 48/80, but Gastric Secretion ccs n/cbO -*-'+■ Time (Days ) Fig. 2.—Graph of total gastric secretion (c.c. 0.1n-HCI) produced by repeated injections at varying intervals of 10 mg. Compound 48/80. Inserted figures are gastric secretory responses (c.c. 0.1n-HC1) to 1 mg. histamine acid phosphate at times marked by accompanying arrows. facial swelling and signs of itchiness are also completely absent. This was repeatedly obtainable in two dogs in which it was attempted. This refractoriness does not, however, involve the secretory response to histamine ; for instance in Fig. 2 on the second day a gastric secretion of 53 c.c. 0.1n-HC1 was obtained with 1 mg. histamine acid phosphate, although immediately afterwards 10 mg. Compound 48/80 failed to elicit any secretion at all. Responsiveness to Compound 48/80, however, is partially restored after 1-2 days (Fig. 2). Discussion The inability of mepyramine to influence the actual release of histamine, while largely eliminating signs and symptoms due to injected or released histamine, is of interest for the interpretation of the mechanism of action of antihistamine drugs in clinical conditions where histamine release is involved. Our experiments suggest
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