THE BLOCKING ACTION OF THE CINCHONA ALKALOIDS AND CERTAIN RELATED COMPOUNDS ON THE CARDIO-INHIBITORY VAGUS ENDINGS OF THE DOG

¹ From the Department of Physiology, New York University College of Dentistry

1. The four principal cinchona alkaloids, three quaternary nitrogen derivatives, and three cupreine derivatives have been investigated with regard to the plasma concentration necessary to block the cardio-inhibitory action of maximal peripheral vagus stimulation in decerebrate and anesthetized dogs.

2. Of the cinchona alkaloids quinidine was effective at the lowest plasma concentration, causing a complete vagus block at concentrations averaging 7.4 mgm. of the sulfate per liter of plasma. Cinchonidine and cinchonine sulfate were effective at average concentrations of 15.5 and 13.3 mgm. per liter respectively, while quinine sulfate was least effective, requiring an average of 19.8 mgm. per liter. Quinine methochloride blocked the vagus at about the same concentration as quinine but quinine ethochloride was effective at about half this concentration. Three other derivatives of cupreine blocked the vagus in the same range of concentration but hydroxy ethylapocupreine showed no effect up to 14.9 mgm. per liter. All of the active drugs decreased the cardioinhibitory effect of vagus stimulation at plasma concentrations considerably below those required to cause complete vagus block.

3. All of these agents caused a depression of blood pressure, the degree of this effect being closely related to the concentration of the infusion fluid. It is in part due to a slowing of the heart rate.

4. The possibility that these agents exert a blocking action on all peripheral neuromotor junctions, autonomic as well as skeletal, is considered.

5. Data on the rates of intravenous administration of these drugs necessary to achieve effective plasma concentrations are presented with a discussion of the factors involved.