MECHANISM OF THE ARTERIAL HYPERTENSION INDUCED BY PAREDRINOL (α-N-DIMETHYL-p-HYDROXYPHENETHYLAMINE

Abstract

In arterial hypertension the cardiac output, the metabolic rate, and the usual blood chemical constituents are essentially normal. Experimental hypertension in man, however, is usually attended by alterations in some of these measurements. Epinephrine produces hypertension in normal subjects, but at the same time it usually increases the heart rate and cardiac output. It elevates the basal metabolism, the blood flow in the muscles, the blood sugar and the blood lactic acid, and also causes great vasoconstriction in the skin vessels. This hypertension is therefore in no way comparable to that observed in disease. The study to be reported indicates that in normal subjects paredrinol sulphate 1 (a-N-dimethyl-p-hydroxyphenethylamine sulphate) produces a type of hypertension which has many features in common with clinical hypertension. For this reason the circulatory adjustments following the administration of this drug are of particular interest.The pharmacology of paredrinol, a sympathomimetic drug closely allied in structure to ephedrine, has been studied extensively in animals. Rein (1, 2), in an investigation of the action of paredrinol on dogs anesthetized with morphine and pernocton, found that both the arterial pressure and the minute volume output of the heart were elevated. The drug acted first on the venous side of the circulation, and produced a greater venous return to the heart by increasing the venous tone and probably by emptying out the liver. This was followed in a few seconds by a slow increase in arterial tone and, shortly thereafter, by a powerful discharge of blood from the abdominal organs, particularly the spleen. Rein claimed that this intense 'discharge of blood from 1 The paredrinol sulphate used in this study was obtained through the courtesy of the Smith, Kline, and French Laboratories. This drug has been reported in the German literature under the trade names "veritol" and " H 75 " (Knoll).the abdominal venous reservoirs indicated that the main cause for the rise in arterial pressure was an increase in venous return to the heart, rather than an increase in peripheral resistance. He demonstrated that the blood flow in the extremities and in the abdominal viscera was never greatly decreased and at times was increased. Since the drug did not cause blanching when introduced into the human skin, he concluded that the capillaries were not constricted and that the arterial tone was increased in the larger vessels.Heymans and Bayless (3), on the basis of experiments conducted on anesthetized dogs, concluded that the vascular effect of the drug was characterized by slight peripheral vasoconstriction and pronounced splanchnic vasoconstriction. When the physiological reflexes for the proprioceptive regulation of blood pressure were depressed by means of barbiturates, they were not restored by paredrinol, even though the blood pressure was raised. Lindner (4), working with isolated cats'-hearts, demonstrated that paredrinol in concentrations of 1 to 1,000,000 increased the frequency and strength of ...

The EFFECT OF BENZEDRINE (Β-Phenylisopropylamine SULPHATE) AND PAREDRINE (Ρ-Hydroxy -Α-Methyl-Phenylethylamine HYDROBROMIDE) ON THE CIRCULATION, METABOLISM AND RESPIRATION IN NORMAL MAN 1

“…These findings are in agreement with those reported by Stead and Kunkel (7) in 2 subjects following the administration of a methyl derivative of paredrine. In 1 instance (Case 12) a decrease in cardiac output and slowing of circulation time due to the action of the vagal reflex were detected.…”

Effect of paredrinol (a-N-dimethyl-p-hydroxyphenethylamine) on sodium nitrite collapse and on clinical shock

“…The effects in normal subjects of the intramuscular administration of paredrinol have been reported (5). The subjects experienced no symptoms except palpitation.…”

“…Such a substance should not cause increased oxygen consumption or widespread chemical changes in the body. From studies of normal subjects it was found that paredrinol 1 (a-N-dimethyl-p-hydroxyphenethylamine) fulfilled several of these requirements (5). Therefore its action was investigated in the collapse induced by sodium nitrite and in that accompanying postural hypotension and acute infectious disease.…”

The Effect of Paredrine on the Venous System. 1

“…The above-described studies established the degree of change in the venous system after the administration of paredrine and to some extent also defined the mechanism of this change. In order to evaluate the importance of changes in the venous system on the genesis of the (2,3,6,12,13), while others regard back-pressure from the heart as the cause (10,11).…”

“…It is most probable that venous constriction is one factor responsible for the rise in venous pressure caused by paredrine. This mechanism is not unique to paredrine, for the venous pressure increase produced by adrenalin in animals and men has been attributed to venous contraction (9,12,13), as has that produced by paredrinol (2,3,4,6). Measurements of the femoral venous pressure after the administration of paredrine show that the increases in pressure occur in these veins also.…”