NATURAL INHIBITORS OF CHOLINESTERASES - IMPLICATIONS FOR ADVERSE DRUG-REACTIONS

Purpose: Acetylcholinesterase and butyrylcholinesterase are two closel y related enzymes important in the metabolism of acetylcholine and ana esthetic drugs, including succinylcholine, mivacurium, and cocaine, Th e solanaceous glycoalkaloids (SGAs) are naturally occurring steroids i n potatoes and related plants that inhibit both acetylcholinesterase a nd butyrylcholinesterase. There are many clinical examples of direct S GA toxicity due to cholinesterase inhibition, The aim of this study wa s to review the hypotheses that (1) SGAs may be the evolutionary drivi ng force for atypical butyrylcholinesterase alleles and that (2) SGAs may adversely influence the actions of anaesthetic drugs that are meta bolized by acetylcholinesterase and butyrylcholinesterase, Source: The information was obtained by Medline search and consultation with expe rts in the study of SGAs and cholinesterases. Principal findings: The SGAs inhibit both acetylcholinesterase and butyrylcholinesterase in nu merous in vitro and in vivo experiments Although accurate assays of SG A levels are difficult, published data indicate human serum SGA concen trations at least ten-fold lower than required to inhibit acetylcholin esterase and butyrylcholinesterase in vitro, However, we review eviden ce that suggests the dietary ingestion of SGAs can initiate a choliner gic syndrome in humans. This syndrome appears to occur at SGA levels l ower 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 atypi cal butyrylcholinesterase alleles, in addition, SGAs may influence the metabolism of anaesthetic drugs and this hypothesis warrants experime ntal investigation.