Abstract
There has been increasing evidence in recent years which indicates that some of the symptoms of anaphylactic shock and other hypersensitivities are due to the liberation of histamine during an antigen antibody reaction. 1-3 For this reason much investigation has been directed toward the discovery of a substance that can counteract the effects of histamine in vivo. 4-8 There has been additional evidence recently that substances having antihistamine properties can do much to alleviate some of the symptoms associated with various types of allergies and other instances of hypersensitivity.
Hetramine which is N,N-dimethylN 1 ben-zyl-N 1 (a-pyrimidyl) ethylene-diamine,∗ is a pyrimidine isostere of a pyridine compound which was found to have antihistamine activity. 8
Hetramine was studied for its antihistamine and antianaphylactic properties in experimental animals. It was found to have an unusually high degree of activity in preventing histamine-induced contractions of isolated intestinal strips. Similarly, it was found to be highly effective in blocking histamine-induced shock in the guinea pig and in preventing fatal anaphylactic shock in hypersensitive animals.
The acute toxicity of hetramine for mice was determined following subcutaneous and oral administration of the compound to respective groups of animals. The LD50 following subcutaneous administration is between 62.5 and 75 mg/kg of mouse weight. Following oral administration, the LD50 was determined to be approximately 300 to 400 mg/kg. The data showing these results may be seen in Table I.
A preliminary experiment on the chronic toxicity of hetramine was carried out by testing the effect of continuous small daily doses in growing rats over a 35-day period. One group of 12 rat weanlings were put on a stock laboratory diet in which was incorporated a quantity of hetramine so that the rats consumed 50 mg/kg of rat weight per day.
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