In vitro interaction of propanidid and suxamethonium with pooled human plasma cholinesterase. A kinetic study.

Human plasma cholinesterase (E.C. 3.1.1.8) was shown to be inhibited by physiological concentrations of propanidid and suxamethonium using a colourimetric assay at 25 degrees C and pH 7.2 unit with butyrylthiocholine as substrate. Propanidid inhibited the enzyme in a non-competitive manner (I50 = 2.0 mmol litre-1; apparent Km = 6.6 X 10(-4) mol litre-1) as did suxamethonium (I50 = 4.4 mmol litre-1; apparent Km = 1.6 X 10(-4) mol litre-1). Combined inhibition produced Km 3.0 X 10(-3) mol litre-1. The binding of these drugs to specific anionic sites in the vicinity of the active centre is thought to result in stereochemical changes in the enzyme. This mechanism and its relevance to the augmentation of the neuromuscular blockade produced by suxamethonium in the presence of propanidid is discussed.