Cholinesterase inhibition by potato glycoalkaloids slows mivacurium metabolism

Background: The duration of action for many pharmaceutical agents is depend ent on their breakdown by endogenous hydrolytic enzymes. Dietary factors th at interact with these enzyme systems may alter drug efficacy and time cour se. Cholinesterases such as acetylcholinesterase (AChE) and butyrylcholines terase (BuChE) hydrolyze and inactivate several anesthetic drugs, including cocaine, heroin, esmolol, local ester anesthetics, and neuromuscular block ing drugs. Natural glycoalkaloid toxins produced by plants of the family So lanaceae, which includes potatoes and tomatoes, Inhibit both AChE and BuChE . Here the authors assess the extent to which two solanaceous glycoalkaloid s (SGAs), alpha-solanine and alpha-chaconine, can alter the effects of neur omuscular 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 vivo c olorimetric cholinesterase assay. In vivo experiments were carried out usin g anesthetized rabbits to test whether SGAs affect recovery from mivacurium -induced paralysis. Results: SGAs inhibited human BuChE at concentrations similar to those foun d in serum of individuals who have eaten a standard serving of potatoes. Co application of SGAs (30-100 nM) with neuromuscular blocking drugs and choli nesterase inhibitors produced additive cholinesterase inhibition. SGA admin istration to anesthetized rabbits inhibited serum cholinesterase activity a nd mivacurium hydrolysis. In addition, SGA prolonged the time needed for re covery from mivacurium-induced paralysis (149 +/- 12% of control; n = 12). Conclusions: These findings support the hypothesis that inhibition of endog enous enzyme systems by dietary factors can influence anesthetic drug metab olism and duration of action. Diet may contribute to the wide variation in recovery time from neuromuscular blockade seen in normal, healthy individua ls.