Abstract

1. In dogs under ether or pentobarbital anesthesia, or pithed, histamine is an active depressor, and its α- and 5-methyl derivatives are about 1/100 as active, while its α-5-dimethyl derivative is only about 1/1000 as active.

2. On isolated rabbit or mouse intestinal strips, histamine and these methyl derivatives are all relatively inactive.

3. On guinea-pig intestinal strips, histamine exerts characteristic contraction effects, and the effects of its α- and 5-methyl derivatives are but 1/100-1/300 as great, with the effects of its α-5-dimethyl derivative even less.

4. While histamine is somewhat less toxic for mice than these methyl derivatives, it is 40 or more times as toxic for guinea-pigs, apparently due to its marked bronchoconstrictor effects in this species.

5. In producing the triple response in the skin of man, histamine is also at least 50 times more active than the methyl derivatives studied.

6. Like histamine, α-methylhistamine was found to orally inactive in dosages as high as 200 mgm. of the dihydrobromide.