The relation of plasma cholinesterases to response to clinical doses of succinylcholine.

Marcz M V S ~ ~L~,XNrS have been introduced during the past decade. Of all these relaxants, succmylcholine is the only drug with a fleeting action. This short duration of action has been ascribed to a rapid enzTmatlc destruction of succinylcholine in the body ( 1, 2). The only enzyme which is known to destroy succinylchohne m man ~s plasma eholinesterase. There are several synonyms for plasma cholmesterase. The enzyme is also caljed serum chohnesterase, pseudo-cholinesterase, or non-specific chohnesterase. The enzyme is distinctly different from acetyl-cholinesterase (or true cholinesterase) (3), which destroys acetylcholine in vivo and which is essential for various functions of the nervous system (4). Plasma cholinesterase is secreted by the liver into the blood (5), but its purpo,~e is unknown. Besides being present in plasma and serum, this esterase occttrs in various tissues (6), for instance in pancreas (7) and in the whate matter of the human brain (8). Plasma eholinesterase differs in its behaviour from species to species (9), and it does not occur in the plasma of all mammals (10). We shall first consider the enzymatic destruction of succinylcholine in vitro. The enzymatic deactivation of succinylcholine is a hydrolysis and proceeds in, two steps (11, 12). First, succinyldicholine is split into succmylmonocholine and choline. Succinylmonocholine is roughly one-twentieth as active m man as succinyldicholine (13, 14). In the'second step, which is a separate reaction, suceinylmonocholine is split into succimc acid and chohne. Either suecinyldicholine or succinylmonocholine combines with the esterase, and during this combination chohne is split off. The combimng power between enzyme and drug (15) is, therefore, an important measure but it is sufficient at the moment to state that the apparent affinity 1 between suceinyldicholine and plasma cholinesterase is twenty times greater than the apparent affinity between sueeinylmonoeholine and the enzyme (16). This is one of the reasons why the reaction occurs in two steps Figuratively speaking, ff the enzyme has a free choice between succinyldicholine and succmylmonocholine, it prefers succmyldicholine However, the enzyme does not always have a free choice. The rate of the enzymatic reaction dep6nds on the following three factors: first, the intrinsic speed, second, the concentrataon of succinylcholme, third, the concentration of the esterase. We have to consider these three factors one by one, First, there is the intrinsic speed with which the enzyme can handle succinyl. choline. This is expressed as a maximum rate of reaction and we state this as