Natural inhibitors of cholinesterases: implications for adverse drug reactions

Purpose

Acetylchomesterase and butyrylcholinesterase are two closely related enzymes important in the metabolism of acetylcholine and anaesthetic drugs, including succinylcholine. mvacunum. and cocaine. The sdanaceous glycoalkaloids (SGAs) are naturally occurring steroids in potatoes and related plants that inhibitboth acetylcholinesterase and butyrylcholinesterase. There are many clinical examples of direct SGA toxicity due to cholinesterase inhibition. The aim of thus study was to review the hypotheses that (I) SGAs may be the evolutionary driving force for atypical butyrytcholinesterase alletes and that (2) SGAs may adversely influence the actions of anaesthetic drugs that are metabolized by acetyicholinesterase and butyrylcholinesterase.

Source

The information was obtained by Medicine search and consultation with experts in the study of SGAs and cholinesterases.

Principal finding

The SGAs inhibrt both acetyicholinesterase and butyrylcholinesterase in numerousin vitro andin vivo experiments. Although accurate assays of SGA levels are difficult, published data indicate human serum SGA concentrations at least ten-fold lower than required to inhibit acetyicholinesterase and butyrylcholinesterasein vitro. However, we review evidence that suggests the detary ingestion of SGAs can initiate a cholinergic syndrome in humans. This syndrome appears to occur at SGA levels lower than those which interfere with anaesthetic drug catabolism. The world distribution of solanaceous plants parallels the distribution of atypical alleles of butyrylcholinesterase and may explain the genetic diversity of the butyrylcholinesterase gene.

Conclusion

Correlative evidence suggests that dietary SGAs may be the driving force for atypical butyrylcholinesterase alleles. In addition. SGAs may influence the metabolism of anaesthetic drugs and this hypothesis warrants experimental investigation.