Influence of acetyl-β-methylcholine, carbamoylcholine, and bis-pyridinium compounds on the activity of acetylcholinesterase

Abstract

The decomposition rate of the substrate acetyl-β-methylcholine by AChE in presence of the antagonists TMB 4, ∗ ∗ [1,1′-trimethylene bis-(4-formylpyridinium bromide)] dioxime. toxogonin, † † Obidoxime = [1,1′-oxydimethylene bis-(4-formylpyridinium chloride)] dioxime. and HS 6 ‡ ‡ [l ,I′-oxydimethylene (2-formyl-3-carbamyl-pyridinium chloride)]. was measured in vitro. The results are compared with those of previous studies using acetylcholine as substrate. Furthermore the reactivating potency of toxogonin on the carbamoylcholine-inhibited enzyme was investigated. The antagonists showed different effects on the substrate decomposition rates of the enzyme, depending on the nature of the substrate. It is concluded that the antagonists as well as the substrates react not only with the active centre of AChE but also with a secondary binding site. In the reactivating reaction of carbamoyl-inhibited AChE, a reaction at a secondary binding site is also involved.