Effects of drugs on partially and completely denervated skeletal muscle of the frog.

The sensitivity of completely denervated and the innervated end-plate regions of partially denervated frog's sartorius muscles to stimulation by drugs has been investigated. The drugs were tested on muscles isolated 12 to 39 days following denervation. On the basis of the results obtained most of the drugs could be put into one of two main groups. The first group included choline, tetramethylammonium, carbachol and decamethonium; these drugs readily stimulated non-denervated muscles, and chronic denervation, either partial or complete, greatly increased the sensitivity of the muscles. The second group included pilocarpine and carbamate of (2-hydroxypropyl) trimethyl ammonium chloride (Bethanechol, U.S.P.). The muscles were relatively insensitive to stimulation by these two drugs. They could stimulate the muscles if applied in high enough concentrations, but the responses thus obtained could not be distinguished from responses produced by similar concentrations of sucrose and chronic denervation did not increase the sensitivity of the muscles to stimulation by these two drugs. Methacholine, like the drugs in the second group, was unable to stimulate the muscles in low concentrations, but chronic denervation rendered the muscles sensitive to stimulation by this drug. Tetraethylammonium presented a completely different pattern of activity which was consistent with a hypothesis that in low doses this drug stimulates skeletal muscle by causing a release of acetylcholine from nerve endings in the muscle.