On the nature of the chemical mediators involved in anaphylactic reactions in mice.

The effects of mepyramine, promethazine, chlorpromazine and lysergic acid diethylamide have been compared on the capillary permeability changes of the skin, produced by histamine, by 5-hydroxytryptamine and by passive cutaneous anaphylaxis in mice. Promethazine, mepyramine and chlorpromazine can inhibit, in decreasing order of activity, the effect of histamine, whilst lysergic acid diethylamide is inactive. Lysergic acid diethylamide and chlorpromazine are equally potent inhibitors of the action of 5-hydroxytryptamine on the peripheral vascular bed, whilst mepyramine is inactive. Promethazine has intermediate activity. Passive cutaneous anaphylaxis is strongly inhibited by chlorpromazine and by promethazine. Mepyramine and lysergic acid diethylamide, each injected alone, affect only weakly the anaphylactic reaction. However, passive cutaneous anaphylaxis is almost completely abolished by the simultaneous injection of the two last antagonists. It is suggested that the anaphylactic reaction in mice is the result of simultaneous release of both mediators, histamine and 5-hydroxytryptamine, each of them strengthening the effect of the other.