OBSERVATIONS ON THE FREQUENCY DEPENDENCE OF SYMPATHETIC GANGLION BLOCKADE

¹ Department of Pharmacology, Schools of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

The ganglion-blocking effects of single dose levels of hexamethonium (C-6), tetraethyl-ammonium (TEA), procaine, hemicholinium (HC-3), and tetramethylammonium (TMA) were studied in the superior cervical ganglion of the cat at stimulus frequencies ranging from 0.5 to 8/second. All compounds except TMA displayed positive linear relationships between degree of block and stimulus frequency. The slopes of this relationship for C-6, TEA, and HC-3 were significantly different from each other at the 1% probability level.

In several experiments TMA block exhibited dependence in the lower portion of the frequency range, but was always independent of frequency between 2 and S/second. At this latter time increasing degrees of frequency dependent facilitation preceded the block.

The discussion analyzes the basis of frequency dependence in ganglion block, for TEA, C-6, and procaine, showing that impulse density per unit time is a primary factor in the positive linear relationship. Differences among the slopes, however, are proposed to result from changes in the effective drug concentration with stimulus frequency. The magnitude and direction of this change are unique for each of the three drugs, and it is suggested that frequency-connected variations in drug-receptor affinities or intrinsic activities are responsible.