Glick (1941), whilst working with various esters of choline, demonstrated that the choline salt of succinic acid was hydrolysed by horse serum and by alkali. Bovet, Bovet-Nitti, Guarino, Longo, and Marotta (1949) and de Beer, Castillo, Phillips, Fanelli, Wnuck, and Norton (1951) showed that succinyldicholine possessed powerful neuromuscular-blocking properties. The latter authors showed that eserine potentiated the paralysis of the cat gastrocnemius caused by succinyldicholine. As compound 49-164, which does not inhibit cholinesterase, produced a similar potentiation they doubted whether cholinesterase was the enzyme responsible for the destruction of succinyldicholine. This seemed worth re-investigation.In the last two or three years many surgeons and anaesthetists have preferred succinyldicholine to other neuromuscular-blocking compounds for many surgical procedures because of its very short duration of action and its freedom from undesirable side-effects. It is ideally suited for administration as an intravenous drip to give a rapidly controllable degree of muscle relaxation. It has also found favour for use with thiopentone in electroconvulsion therapy (Arnold, B6ck-Greisau, and Ginzel, 1951; Richards and Youngman, 1952).Mayrhofer (1952) has, however, stated that succinyldicholine is stable in solution for several weeks outside the refrigerator and also when mixed with thiopentone. This was surprising, since succinyldicholine is unstable in alkaline solution (Glick, 1941) and the pH of thiopentone solution is around 11.0. It thus seemed desirable to re-examine Mayrhofer's claims. The hydrolysis of succinyldicholine at elevated temperatures, in alkaline solutions, and by pseudo-cholinesterase, has accordingly been studied. A quantitative comparison has also been made between succinyldicholine and its first hydrolysis product, succinylmonocholine, which still preserves a degree of neuromuscular-paralysing activity.
METHODSToxicity.-Groups of 5 or 10 albino mice of either sex were used, injections being made into the tail vein.Action on Nerve-Muscle Preparations.-The isolated rat diaphragm-phrenic nerve preparation of BUlbring (1946) was used (a) as an in vitro test for concentration of succinyldicholine, and (b) for comparison of the concentrations of succinyldicholine and succinylmonocholine to give equal neuromuscular-paralysing action. The isolated organ was immersed in a Ringer-Locke solution in a 100 ml. bath, and square stimuli of 2 V. and of 0.23 msec. duration were applied at 5/min. to the nerve. Drugs were added from a tuberculin syringe and left in contact with the diaphragm for 3 min. This was followed by two washes with Ringer-Locke at 3 and 6 min. respectively, giving a total cycle of 10 min. In 3 min., 50% paralysis of the diaphragm twitch was produced by a concentration of about 15.0 zg./ml. of succinyldicholine.Tests in vivo were performed on cats and rabbits of either sex. The cats were anaesthetized with pentobarbitone sodium (usually 40 mg./kg. i.p.), and the rabbits with urethane (am...
