Inhibition of human serum and rabbit muscle cholinesterase by local anesthetics.
The effects of tertiary amine local anesthetics (procaine, mepivacaine, lidocaine, tetracaine, dibucaine, and bupivacaine) and chlorpromazine were investigated for rabbit muscle acetylcholinesterase and human serum cholinesterase. The muscle enzyme was poorly inhibited by local anesthetics containing an amide linkage. The serum cholinesterase was inhibited by all those compounds, their relative potencies being proportional to their octanol/water partition coefficients. The dissociation constants of tetracaine and procaine, ester anesthetics, were 1000-fold and 100-fold, respectively, that which would be expected from their partition coefficient basis respective to the other amide anesthetics. Procaine showed competitive inhibition of serum cholinesterase, whereas for most anesthetics a mixed type of inhibition was observed. Procaine probably binds at the main anionic site, while the other positively charged anesthetics bind to either the catalytic centre or to the peripheral or modulator anionic site, modifying the kinetic behaviour of cholinesterase as has been demonstrated by the appearance of negative cooperativity for binding to the substrate.
Pérez-Guillermo
F
F
Departamento de Bioquímica, Facultad de Biología, Universidad de Murcia, Spain.
Delgado
E M
EM
Vidal
C J
CJ
D000110:Acetylcholinesterase / Q000097:blood / Q000302:isolation & purification; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D009132:Muscles / Q000201:enzymology*; D011817:Rabbits; D012995:Solubility
D000779:Anesthetics, Local; D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase