CIRCULATORY PROPERTIES OF iso-THIOUREAS, GUANIDINES, iso-UREAS AND AMIDINES

¹ Department of Medicine, University of Otago, New Zealand

1. Attention is drawn to the lower members of four series of amidine derivatives —iso-thioureas, guanidines, iso-ureas and the amidines themselves—which provide close analogies in their pharmacological as well as in their chemical behaviour.

2. The present report deals especially with the circulatory properties of salts of S-methyl iso-thiourea, S-ethyl iso-thiourea, methylguanidine, ethylguanidine, as.-dimethylguanidine, benzylguanidine, O-methyl iso-urea, O-ethyl iso-urea, acetamidine, propionamidine and n-butyramidine, which differ only in the nature of the substituent attached to the amidine group.

3. All the above substances raise the blood pressure of anaesthetized dogs, produce vasoconstriction in perfused pithed rat hind-quarters even after treatment with ergotoxine, and contract atropinized gut; they appear to stimulate smooth muscle directly.

4. With few exceptions the above substances enhance the pressor action of adrenaline in dogs and, under the experimental conditions referred to in the text, all substances either increase or diminish the response of perfused rat blood vessels to injections of adrenaline. Such effects on the sensitivity to adrenaline are therefore located peripherally. In the doses employed sensitization of rat blood vessels to adrenaline is the more usual effect but one substance, benzylguanidine, reduces the sensitivity.

5. They increase pulmonary ventilation.

6. Their effect on the heart rate is not uniform in the dog but the most usual effect is slowing.

7. It is suggested that these amidine derivatives and amidines of lower molecular weight, which are closely related chemically, form a well-defined pharmacological group.

We are indebted to the Medical Research Council of New Zealand for a Grant and to the Editors of the Journal for eliminating an ambiguity.