Hydrolysis of Succinylcholine Salts

Abstract

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...

Interaction at end-plate receptors between different choline derivatives

“…not subject to enzymic hydrolysis a t the myoneural junction. Succinylcholine is known to be inactivated fairly rapidly vivo, b u t according to Fraser (1954) the enzymic hydrolysis of this substance in vitro is slow compared with th a t of Ach, and almost entirely due to serum-esterase, while the specific tissue enzyme appears to have little effect on succinylcholine.…”

The relationship between the level of cholinesterase in plasma and the action of suxamethonium in animals

“…As far as laboratory animals are concerned it is well established that inhibitors of cholinesterase potentiate the action of suxamethonium (Brucke, 1956) but Keleman & Volle (1966) who studied the effect of anticholinesterase 2-diethoxyphosphinylthioethyldimethylamine acid oxalate (217 AO) on the action of suxamethonium in cats, found that there was no linear relationship between the effectiveness of suxamethonium and reduction of the level of cholinesterase in plasma and that considerable inhibition of the enzyme in plasma was required before potentiation of the action of suxamethonium occurred. Furthermore, Fraser (1954) noted that inhibition of cholinesterase in the plasma of cats by physostigmine was maximal in less than 10 min while potentiation of the action of suxamethonium was greatest one hour after the injection of the anticholinesterase.…”

The Influence of Changes in Acid-Base Balance on Neuromuscular Blockade in Cats

“…However, Gamstorp and Vinnars (1963), using electrical rather than mechanical responses, reported that paralysis produced in rabbits was enhanced by severe respiratory acidosis but was not significantly influenced by respiratory alkalosis, metabolic acidosis or by alkalosis. These authors suggested that the effect of respiratory acidosis could be attributed to decreased enzymatic hydrolysis of suxamethonium at lowered pH (Augustinsson, 1948;Fraser, 1954). Baraka (1967) attributed a similar but small effect in man…”