THE NEUROMUSCULAR PHARMACOLOGY OF GERMINE-3-ACETATE AND GERMINE-3,16-DIACETATE

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

Germine-3-acetate (GMA) and germine-3,16-diacetate, veratrum derivatives reported to be effective in the treatment of myasthenia gravis, were studied on cat coleus nerves and muscles. Neither agent has any effect on unstimulated preparations, but both increase the strength of neurally stimulated innervated and 48-hour denervated muscles and of directly stimulated, curare-treated and 14- to 16-day denervated muscles. The threshold dose of GMA is approximately the same in all of these, and in all of them the increase in contraction strength is associated with repetitive muscle potentials. The neural effects of GMA were studied by recording from the ventral roots of the soleus nerve. GMA, in approximately the same dose range as that which increases contraction strength, causes the neural response to a single stimulus to become repetitive. The repetitive activity develops in axons stimulated at all frequencies below 20 Hz and is decreased or abolished by stimulus frequencies greater than this. Neuromuscular blocking doses of d-tubocurarine or GMA abolish muscle electrical activity but do not affect the repetitive activity in the nerve. The relationship between GMA-induced nerve and muscle repetition was studied by simultaneously recording the nerve and muscle activities of single motor units. Most commonly we observed synchronous nerve and muscle repetition, in which the nerve repetitive potentials preceded the muscle repetitive potentials, but in a few experiments repetitive muscle potentials were observed to occur in the absence of repetitive nerve potentials. Therefore, GMA seems to have the capacity to act on both nerve and muscle, but in innervated preparations its action on the muscle occurs only when the muscle is not responding to activity transmitted from the nerve. Germine-3,16-diacetate is qualitatively similar to GMA but is approximately 7 times less potent.