POTENTIATION OF THE ACTIVITY OF HYPOTENSIVE DRUGS: EFFECT OF SEVERAL SYNTHETIC COMPOUNDS ON SIX HYPOTENSIVE AGENTS IN HYPERTENSIVE RATS AND NORMOTENSIVE DOGS

¹ LaW all Memorial Laboratory of Pharmacology and Biochemistry, Philadelphia Collegeof Pharmacy and Science, Philadelphia, Pennsylvania
² LaWall Memorial Laboratory of Pharmacology and Biochemistry, Philadelphia College of Pharmacy and Science, Philadelphia, Pennsylvania

Four synthetic compounds of diverse chemical structure (SKF 525-A, Lilly 18947, NDR A-1358 and NDR A-2435) were shown to enhance markedly the intensity and duration of the depressor response to reserpine, rescinnamine, hydralazine, mecamylamine, 2-(N,N-diallylcarbamylmethyl) -aminomethyl-1,4-benzodioxan and mannitol hexanitrate in unanesthetized chronic hypertensive rats. Inthe doses employed, the 4 potentiating agents exerted no sedative or blood pressure lowering effects when administered alone.

Subthreshold doses of the 6 hypotensive drugs produced a significant reduction of systolic pressure when administered to hypertensive rats pretreate with either SKF 525-A, Lilly 18947, NDR A-1358 or NDR A-2435. It was also found that injection of the potentiating agents after the blood pressure reducing activity of the hypotensive drugs had largely terminated evoked a renewed and markedly increased depressor response in hypertensive rats.

Essentially similar results were obtainel when several of these experiments were performed with unanesthetized normotensive dogs.

Indications are presented that potentiation of hypotensive drug activity by SKF 525-A and certain other synthetic compounds (Lilly 18947, NDR A-1358 and NDR A-2435) cannot be accounted for solely on the basis of the retardation of drug biotransformation.