THE PHARMACOLOGICAL ACTION OF BENZAMIDINES AND BENZAMIDOXIMES

¹ From the Department of Pharmacology, Oxford

1. When single doses of the benzamidines V147 or V187 are given intravenously to experimental animals they produce:

a. A rise of blood pressure if the dose is small

b. A fall of blood pressure due to peripheral vasodilatation if the dose is larger than 5 mg./kg.

C. A stimulation of respiration, partly due to the fall of blood pressure and partly due to a central action.

d. Vomiting when given to pigeons.

e. Death due to respiratory failure after excessive doses.

2. V186, a benzamidoxime, resembles V147 and V187 in having no direct action on the heart. It is much less active pharmacologically and this difference has been demonstrated on the smooth muscle of the walls of arterioles, of the spleen and of the intestine ; in the respiratory and vomiting centres of the medulla, and in the growth rate of young rats. This benzamidoxime is therefore less toxic in acute experiments than the analogous benzamidine.

3. V187 has no appreciable effect in single injections on the blood sugar, salivary secretion, spinal reflexes or capillary permeability. It may be infused slowly into the anaesthetized cat at a rate of up to 5 mg./minute without alteration of blood pressure, respiration or intestinal movement: this rate of absorption is unlikely to be reached after local application of the drug to wounds

4. V187 has been fed to rabbits and rats in a dose of 0.2 g./kg./day for two weeks without affecting the blood count, liver or kidney function.

5. The relation between the structure of guanidine, amidine and thiourea derivatives and their pharmacological actions is discussed.