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.

    5/10 (page 511)
    Results The subcutaneous injection of 10 mg. Compound 48/80 into a dog always pro¬ duced signs of severe itchiness, facial swelling, and secretion of gastric juice lasting 1-2 hours (Fig. 1). The facial swelling was particularly marked in the bristle area near the mouth, the eyelids, and the pinna of the ear ; these areas also showed considerable erythema. Oedema and erythema of other regions was not observed, except for the nipple area in one animal. The gastric secretion produced by this dose of Compound 48/80 corresponded to that elicited by 1-2 mg. histamine acid phosphate. Although the facial swelling and the signs of pruritus were almost entirely abolished by mepyramine, the gastric secretion was never diminished and usually considerably increased (Fig. 1, Table I). Further evidence that this dose of mepyramine was effective against either injected histamine or the circulatory depressor action of a liberator was that in the anaesthetized animal the depressor action of the liberator was reduced, and that in an unanaesthetized animal weal formation by intradermal injections of histamine was antagonized. It follows that an otherwise effective dose of mepyramine did not reduce the amount of histamine released by Compound 48 / 80. The question now arises why the gastric secretion should actually be increased by mepyramine. The possibility that under these circumstances mepyramine alters the response of the gastric glands to histamine was excluded by demonstrating that in the same four dogs the gastric secretory response to injected histamine was not significantly altered by the same dose of mepyramine (Table II). Another explanation, however, may be that associated with the swelling and oedema of the face there is an oedema of the gastric mucosa, which is known to reduce gastric TABLE II EFFECT OF MEPYRAMINE ON GASTRIC SECRETION PRODUCED BY HISTAMINE Histamine, 1 mg. subcutaneously. Mepyramine, 2 mg./kg. subcutaneously given 15 min. before histamine Dog c.c. Histamine a 0.1n-HC1 produced by Histamine + Mepyramine b Ratio bla Spot 22.1 25.0 1.13 Dusky • • • • # # 34.4 23.1 0.67 Jackie 84.6 65.1 0.77 Blackie .. • • 38.0 51.4 1.35 Total • • 179.1 164.6 Av. ratio = 1.02 secretion (Ricketts, Kirsner, and Palmer, 1949). The action of mepyramine in preventing this oedema would then allow the gastric secretion to proceed unimpeded during a period when it would otherwise be inhibited. Some support for this was obtained by the observation that the gastric mucosa was congested and oedematous to direct inspection in a dog anaesthetized after injection of Com¬ pound 48/80; also, in our unanaesthetized dogs, in the absence of mepyramine 2L