Summary
-
1.
The influence of the 2 alkane-bis-onium compounds hexafluorenium (HFl) and hexamethonium (C6) on human plasma cholinesterase (ChE) was studied with respect to the type of inhibition.
-
2.
HFl and C6 are reversible inhibitors of ChE. The inhibitory potency of HFl (pI50=6.96; Ki=2.4×10−9) is about 40000-fold higher than that of C6 (pI50=2.4; Ki=6.7×10−2).
-
3.
The kinetic analysis displayed a competitive (C6) and a non-competitive (HFl) mechanism of action.
-
4.
The inhibition of ChE by C6 is induced by a binding of C6 to the anionic site of the active center thus impairing the primary formation of the enzyme-substrate complex. HFl, however, is most probably bound to anionic side receptors in the vicinity of the active center; by that a conformational change of the enzyme protein is induced impairing the acylation step of the esteratic site.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Britton, R. M., Figueroa, M.: Hexafluorenium bromide: current status and a review. Anesth. Analg. Curr. Res. 52, 100–105 (1973)
Foldes, F. F., Hilmer, N. R., Molloy, R. E., Monte, A. P.: Potentiation of the neuromuscular effect of succinylcholine by hexafluorenium. Anesthesiology 21, 50–58 (1960a)
Foldes, F. F., Molloy, R. E., Zsigmond, E. K., Zwartz, J. A.: Hexafluorenium: its anticholinesterase and neuromuscular activity. J. Pharmacol. exp. Ther. 129, 400–404 (1960b)
Knedel, M., Böttger, R.: Eine kinetische Methode zur Bestimmung der Aktivität der Pseudocholinesterase (Acetylcholin-acylhydrolase E.C. 3.1.1.8). Klin. Wschr. 45, 325–327 (1967)
Lüllmann, H., Ohnesorge, F. K., Tonner, H. D., Wassermann, O., Ziegler, A.: Influence of alkane-bis-onium compounds upon the activity of the AChE and upon its inhibition by DFP. Biochem. Pharmacol 20, 2579–2586 (1971)
Michaelis, L., Menten, M. L.: Die Kinetik der Invertinwirkung. Biochem. Z. 49, 333–369 (1913)
Mutschler, E., Springer, J., Wassermann, O.: Guanylhydrozones, another class of monoamin oxidase inhibitors. Biochem. Pharmacol. 19, 9–15 (1970)
Schuh, F. T.: Pseudocholinesterase activity of human whole blood, bank blood, and blood protein solutions. Anaesthesist 24, 103–106 (1975a)
Schuh, F. T.: Influence of ketamine upon human plasma cholinesterase. Brit. J. Anaesth. 47, 1315–1319 (1975b)
Tonner, H. D.: Kinetische Untersuchungen über die Protektion der Acetylcholinesterase vor der Diisopropylfluorophosphat-Vergiftung durch Polymethylen-bis-onium Verbindungen. Thesis, Christian-Albrechts-Universität, Kiel 1971
Webb, J. L.: Enzyme and metabolic inhibitors, vol. I. New York-London: Academic Press 1963
Wilson, I. B.: Conformational changes in acetylcholinesterase. Ann. N.Y. Acad. Sci. 144, 644–674 (1967)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schuh, F.T. Interaction of hexafluorenium with human plasma cholinesterase in comparison with hexamethonium. Naunyn-Schmiedeberg's Arch. Pharmacol. 293, 11–13 (1976). https://doi.org/10.1007/BF00498865
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00498865