The Effect of Antihistaminics on Mice Hypersensitive to H. Pertussis Vaccine *

In connection with several recent publications"' on reaction in children after injection of H. pertussis vaccine, it might be of interest to report our own observations on the action of antihistaminic drugs on mice sensitized by this vaccine. In a previous publication8 it was reported that treatment of mice with H. pertussis vaccine renders these animals highly sensitive to histamine. These findings were extended in a recent paper by Parfentjev and Schleyer.10 Dependent on the vaccine dose and the mice selected for this type of experiment, the LD50 of histamine in sensitized mice was found to be 1/306 to 1/120'° that of non-sensitized animals. It has also been shown8 that antihistaminic drugs, e.g. Bromothen [N,N-dimethyl-N'(2-pyridyl)-N'(5bromo-2-thenyl)-ethylene-diamine hydrochloride],' counteracted the histamine effect in sensitized mice, thus indicating that this technique might be used for the evaluation of anti-histaminic agents. A further advantage of using experimentally sensitized mice might be seen in the fact that the immiunizing effect of H. pertussis vaccine also produced a hypersensitiveness of the animals to H. pertussis protein-antigen.' This offered the possibility of measuring the effect of antihistaminic drugs in mice against both histamine shock and anaphylaxis using the same sensitization in both instances. In order to determine the usefulness of the mouse assay in the evaluation of antihistaminics, a number of experiments were carried out with the antihistaminic drug Thephorin, described by Lehmann' and Lehmann, Randall, and Hagan;' this substance, the tartrate of 2-methyl-9-phenyl-2,3,4,9tetraphydro-1-pyridindene, appeared interesting because it bears no chemical relationship to any existing histamine antagonist. The results of our experiments are presented in this paper.