BACKGROUND: The duration of action for many pharmaceutical agents is dependent on their breakdown by endogenous hydrolytic enzymes. Dietary factors that interact with these enzyme systems may alter drug efficacy and time course. Cholinesterases such as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) hydrolyze and inactivate several anesthetic drugs, including cocaine, heroin, esmolol, local ester anesthetics, and neuromuscular blocking drugs. Natural glycoalkaloid toxins produced by plants of the family Solanaceae, which includes potatoes and tomatoes, inhibit both AChE and BuChE. Here the authors assess the extent to which two solanaceous glycoalkaloids (SGAs), alpha-solanine and alpha-chaconine, can alter the effects of neuromuscular blocking drugs and cholinesterase inhibitors in vivo and in vitro. METHODS: Inhibition of purified human AChE and BuChE by SGAs, neuromuscular blocking drugs, and cholinesterase inhibitors was assessed by an in vitro colorimetric cholinesterase assay. In vivo experiments were carried out using anesthetized rabbits to test whether SGAs affect recovery from mivacurium-induced paralysis. RESULTS: SGAs inhibited human BuChE at concentrations similar to those found in serum of individuals who have eaten a standard serving of potatoes. Coapplication of SGAs (30-100 nm) with neuromuscular blocking drugs and cholinesterase inhibitors produced additive cholinesterase inhibition. SGA administration to anesthetized rabbits inhibited serum cholinesterase activity and mivacurium hydrolysis. In addition, SGA prolonged the time needed for recovery from mivacurium-induced paralysis (149 +/- 12% of control; n = 12). CONCLUSIONS: These findings support the hypothesis that inhibition of endogenous enzyme systems by dietary factors can influence anesthetic drug metabolism and duration of action. Diet may contribute to the wide variation in recovery time from neuromuscular blockade seen in normal, healthy individuals.
BACKGROUND: The duration of action for many pharmaceutical agents is dependent on their breakdown by endogenous hydrolytic enzymes. Dietary factors that interact with these enzyme systems may alter drug efficacy and time course. Cholinesterases such as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) hydrolyze and inactivate several anesthetic drugs, including cocaine, heroin, esmolol, local ester anesthetics, and neuromuscular blocking drugs. Natural glycoalkaloid toxins produced by plants of the family Solanaceae, which includes potatoes and tomatoes, inhibit both AChE and BuChE. Here the authors assess the extent to which two solanaceous glycoalkaloids (SGAs), alpha-solanine and alpha-chaconine, can alter the effects of neuromuscular blocking drugs and cholinesterase inhibitors in vivo and in vitro. METHODS: Inhibition of purified humanAChE and BuChE by SGAs, neuromuscular blocking drugs, and cholinesterase inhibitors was assessed by an in vitro colorimetric cholinesterase assay. In vivo experiments were carried out using anesthetized rabbits to test whether SGAs affect recovery from mivacurium-induced paralysis. RESULTS: SGAs inhibited human BuChE at concentrations similar to those found in serum of individuals who have eaten a standard serving of potatoes. Coapplication of SGAs (30-100 nm) with neuromuscular blocking drugs and cholinesterase inhibitors produced additive cholinesterase inhibition. SGA administration to anesthetized rabbits inhibited serum cholinesterase activity and mivacurium hydrolysis. In addition, SGA prolonged the time needed for recovery from mivacurium-induced paralysis (149 +/- 12% of control; n = 12). CONCLUSIONS: These findings support the hypothesis that inhibition of endogenous enzyme systems by dietary factors can influence anesthetic drug metabolism and duration of action. Diet may contribute to the wide variation in recovery time from neuromuscular blockade seen in normal, healthy individuals.
Authors: Brian C Geyer; Latha Kannan; Pierre-Emmanuel Garnaud; Clarence A Broomfield; C Linn Cadieux; Irene Cherni; Sean M Hodgins; Shane A Kasten; Karli Kelley; Jacquelyn Kilbourne; Zeke P Oliver; Tamara C Otto; Ian Puffenberger; Tony E Reeves; Neil Robbins; Ryan R Woods; Hermona Soreq; David E Lenz; Douglas M Cerasoli; Tsafrir S Mor Journal: Proc Natl Acad Sci U S A Date: 2010-11-08 Impact factor: 11.205
Authors: Samuel P Fletcher; Brian C Geyer; Amy Smith; Tama Evron; Lokesh Joshi; Hermona Soreq; Tsafrir S Mor Journal: Plant Mol Biol Date: 2004-05 Impact factor: 4.076
Authors: Rosilene R Kaizer; Adriane C da Silva; Vera M Morsch; Maisa C Corrêa; Maria R C Schetinger Journal: Neurochem Res Date: 2004-12 Impact factor: 3.996
Authors: Katherine E Larrimore; Matthew Barcus; Latha Kannan; Yang Gao; Chang-Guo Zhan; Stephen Brimijoin; Tsafrir Mor Journal: Chem Biol Interact Date: 2012-09-20 Impact factor: 5.192
Authors: Ella H Sklan; Alexander Lowenthal; Mira Korner; Ya'acov Ritov; Daniel M Landers; Tuomo Rankinen; Claude Bouchard; Arthur S Leon; Treva Rice; D C Rao; Jack H Wilmore; James S Skinner; Hermona Soreq Journal: Proc Natl Acad Sci U S A Date: 2004-04-01 Impact factor: 11.205
Authors: I Manoharan; A Kuznetsova; J D Fisk; R Boopathy; O Lockridge; S Darvesh Journal: J Neural Transm (Vienna) Date: 2007-02-22 Impact factor: 3.850