THE EFFECTS OF GERMINE-3-ACETATE ON NEUROMUSCULAR TRANSMISSION

¹ Department of Pharmacology, Georgetown University, Schools of Medicine and Dentistry, Washington, D. C.

Germine-3-acetate (GMA) is a veratrum derivative that causes repetitive nerve and muscle activity, increases skeletal muscle contraction strength, antagonizes neuromuscular block by d-tubocurarine and succinylcholine and has been reported to be effective in the treatment of myasthenia gravis. The effects of GMA on neuromuscular transmission were studied in the in vitro frog sartorius nerve muscle preparation. GMA has no effect on unstimulated preparations but causes the response evoked by a single nerve or muscle stimulus to become repetitive. Concentrations of GMA which cause repetitive nerve and muscle activity (1-20 µg/ml) do not change miniature end-plate potential amplitude or frequency in either normal or high Mg⁺⁺-low Ca⁺⁺ Ringer's solution. These concentrations of GMA do not change the amplitude, quantum size, quatum content, time course or primary potentiation of end-plate potentials recorded from preparations in which neuromuscular transmission is depressed by high Mg⁺⁺-low Ca⁺⁺ Ringer's solution. Accordingly, the production of repetitive nerve activity by GMA is not a consequence of increased transmitter release or of intensification or prolongation of transmitter action. GMA apparently represents a new type of neuromuscular reagent in that it profoundly affects neuromuscular function but does not influence neuromuscular transmission, i.e., GMA does not alter the processes involved in transmitter release, action or removal.