NATURE OF THE HYPOTENSIVE ACTION OF A THIOPHANIUM DERIVATIVE (RO 2-2222) IN DOGS

¹ Research Division of the Cleveland Clinic Foundation and the Frank E. Bunts Educational Institute, Cleveland, Ohio

Ro 2-2222 was found to have a potent but brief hypotensive action when given intravenously in dogs. Refractoriness often developed when repeated small doses were given but sustained hypotension could be produced by continuous infusion. With moderate fall in blood pressure, Ro 2-2222 had little effect upon vascular reactivity and failed to augment responses as do TEAC and hexamethonium bromide. Large doses were often lethal and, when not, shock developed with accompanying loss of vascular reactivity. Given subcutaneously or intramuscularly, Ro 2-2222 produced sustained fall in blood pressure in normal dogs but was without effect given orally. Its hypotensive action was more marked in neurogenic hypertensive than in normal dogs but this enhancement was not so striking as with TEAC.

1-Hydrazinophthalazine did not influence the hypotensive action of Ro 2-2222. Depressor responses were occasionally reduced or reversed by Priscoline. Benadryl did not appreciably modify responses to Ro 2-2222 when histamine responses were largely abolished.

The hypotensive action of Ro 2-2222 was not diminished by section of the spinal cord at C₆, removal of the paravertebral sympathetic chains or ganglionic blockade with TEAC or hexamethonium bromide. It had a strong vasodilator effect in the perfused denervated dog's leg when TEAC was entirely pressor.

From these observations it is concluded that Ro 2-2222 lowers arterial pressure in dogs primarily by direct vasodilation; blockade of sympathetic ganglia and release of histamine are considered to play a minor part in hypotensive responses to small doses.

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