Inhibition of synaptosomal enzymes by local anesthetics

Hasidah Mohd. Sidek, Cynthia Nyquist-Battie, Garret Vanderkooi

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The effects of tertiary amine local anesthetics (procaine, lidocaine, tetracaine and dibucaine) and chlorpromazine were investigated for three enzyme activities associated with rat brain synaptosomal membranes, i.e., (Na+ + K+)-ATPase (ouabain-sensitive), Mg2+-ATPase (ouabain-insensitive) and acetylcholinesterase. Approximately the same concentrations of each agent gave 50% inhibition of both ATPase, for example 7.9 and 10 mM tetracaine for Mg2+-ATPase and (Na+ + K+)-ATPase, respectively; these concentrations are 10-fold higher than required for inhibition of mitochondrial F1-ATPase. The relative inhibitory potency of the several agents was proportional to their octanol/water partition coefficients. Acetylcholinesterase was inhibited by all agents tested, but the ester anesthetics (procaine and tetracaine) were considerably more potent than the others after correction for partition coefficient differences. For tetracaine, 0.18 mM gave 50% inhibition and showed competitive inhibition on a Lineweaver-Burk plot, but for dibucaine a mixed type of inhibition was observed, and 0.63 mM was required for 50% inhibition. Tetracaine evidently binds at the active site, and dibucaine at the peripheral or modulator site, on this enzyme.

Original languageEnglish
Pages (from-to)26-31
Number of pages6
JournalBBA - General Subjects
Volume801
Issue number1
DOIs
Publication statusPublished - 7 Sep 1984
Externally publishedYes

Fingerprint

Tetracaine
Local Anesthetics
Dibucaine
Adenosine Triphosphatases
Enzymes
Ca(2+) Mg(2+)-ATPase
Procaine
Ouabain
Acetylcholinesterase
Octanols
Proton-Translocating ATPases
Chlorpromazine
Enzyme activity
Lidocaine
Modulators
Amines
Anesthetics
Rats
Brain
Catalytic Domain

Keywords

  • (Rat brain synaptosome)
  • Acetylcholinesterase
  • ATPase
  • Enzyme inhibition
  • Local anesthetics

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Inhibition of synaptosomal enzymes by local anesthetics. / Mohd. Sidek, Hasidah; Nyquist-Battie, Cynthia; Vanderkooi, Garret.

In: BBA - General Subjects, Vol. 801, No. 1, 07.09.1984, p. 26-31.

Research output: Contribution to journalArticle

Mohd. Sidek, Hasidah ; Nyquist-Battie, Cynthia ; Vanderkooi, Garret. / Inhibition of synaptosomal enzymes by local anesthetics. In: BBA - General Subjects. 1984 ; Vol. 801, No. 1. pp. 26-31.
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