THE ACTION OF PICROTOXIN AND OF NIKETHAMIDE (DIETHYLAMIDE OF PYRIDINE-3-CARBOXYLIC ACID) ON NEUROMUSCULAR CONDUCTIVITY

¹ Department of Pharmacology and Biological Chemistry, Catholic University of Chile, Santiago de Chile, Chile

In cats anesthetized with nembutal a study is made of the effect of picrotoxin on indirect contraction of the quadriceps femoris (Section I), the effect of nikethamide (coramine) on the indirectly stimulated soleus and quadriceps muscles (Section II, A), the effect of nikethamide on the response of muscle stimulated by the action of acetylcholine (Section II, C), and on the response of directly stimulated muscle (Section II, D).

When picrotoxin is injected during indirect stimulation of muscle it has either no effect at all or else only a slight depression of muscular contraction when the stimuli are of frequencies greater than 32 per second. (Fig. 1).

Nikethamide increases the development of tension of a muscle stimulated indirectly at low frequencies (fig. 2A and 2B) and produces a depression of muscular contraction when the stimuli are of higher frequencies (fig. 1 and 2C).

Nikethamide depresses the first stage of neuromuscular transmission (fig. 3A) and also depresses the amplitude of the contractions of a muscle stimulated indirectly every 15 seconds with a frequency of 500 stimuli per second. The first stages, namely 1, 2, 3a, 3b, and 3c, undergo a series of changes which are described in Section II A (fig. 3B). The action of curare (fig. 4) and the action of prostigmine (fig. 5) are reinforced by the action of nikethamide.

The contractions produced by acetylcholine in a muscle sensitized by denervation are reinforced by the effect of nikethamide. (Fig. 6).

Nikethamide does not alter the curve of the contraction of a directly stimulated muscle so long as there is not fatigue (fig. 7A), but depresses the curve in the presence of muscular fatigue. (Fig. 7B). This difference is discussed.

These results are analyzed in the light of our present knowledge of the chemical theory of nerve impulse transmission.