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

  • Paton, William D. M.
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 INFLUENCE OF AN ANTIHISTAMINE DRUG ON THE RELEASE OF HISTAMINE IN THE UNANAESTHETIZED DOG BY W. D. M. PATON AND M. SCHACHTER From the National Institute for Medical Research, Mill Hill, London, N.W.7 (Received May 18, 1951) There is evidence that the histamine content of the blood increases under a variety of conditions, including anaphylaxis, and after the administration of adrenaline, the wetting agent Tween 20, and a variety of organic bases (Feldberg, 1941 ; Krantz, Carr, Bird, and Cook, 1948 ; Macintosh and Paton, 1949). Little information has been acquired, however, about the ability of the antihistamine com¬ pounds to influence the process of histamine release. Wells, Morris, and Dragstedt (1946), in only two experiments showed that, despite protection with benadryl, the anaphylactic reaction was accompanied by high levels of plasma histamine. This indicates that benadryl does not prevent the release of histamine in anaphylaxis. Staub (1946) claims, however, that the release of histamine into the blood after administration of adrenaline to man is prevented by antistin. Grossman and Robertson (1948), using the gastric secretion of the total stomach pouch of dogs as an index of released histamine, observed that the gastric secretion following administration of Tween 20 was greatly reduced by benadryl. The interpretation of these results is difficult, particularly since neither antistin (Reuse, 1948) nor benadryl (Schild, 1947) is a specific antihistamine, and since the total pouch used by Grossman has unusual secretory characteristics (Woodward, Dragstedt, Tovee, Oberhelman, and Neal, 1945). So much importance, however, both theoretical and practical, attaches to any drug which can modify the process of histamine liberation that we have further examined the problem. As an index of histamine release we measured the hydrochloric acid secreted by the intact cannu- lated stomach of trained dogs. Mepyramine maleate (neoantergan) was selected as an antihistamine because of its high specificity (Schild, 1947 ; Reuse, 1948). The histamine liberator Compound 48/80, a condensation product of p-methoxy- phenylethylmethylamine and formaldehyde (Baltzly, Buck, de Beer, and Webb, 1949 ; Paton, 1951), provided a simple means of obtaining a gradable histamine¬ releasing action without tissue destruction or signs other than those due to histamine release. In a few experiments, another histamine liberator, propamidine (Macintosh and Paton, 1949) was used. Methods Four dogs, weighing between 10 and 20 kg., trained to stand quietly in a frame for hours, were equipped with gastric cannulae made of monel metal. Under these conditions the gastric reaction was always alkaline unless we deliberately took measures