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Effect of amiodarone on Na + ‐, K + ‐ATPase and Mg 2+ ‐ATPase activities in rat brain synaptosomes
Author(s) -
Rao K. S. Prasada,
Rao S. B.,
Camus Ph.,
Mehendale H. M.
Publication year - 1986
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.290040210
Subject(s) - amiodarone , ouabain , chemistry , atpase , medicine , endocrinology , mechanism of action , pharmacology , phosphorylation , biochemistry , sodium , enzyme , in vitro , organic chemistry , atrial fibrillation
Amiodarone hydrochloride is a diiodinated antiarrhythmic agent widely used in the treatment of cardiac disorders. With the increasing use of amiodarone, several untoward effects have been recognized and neuropathy following amiodarone therapy has recently been reported. The present studies were carried out to study the effect of amiodarone on rat brain synaptosomal ATPase in an effort to understand its mechanism of action. Na + , K + ‐ATPase and oligomycin sensitive Mg 2+ ATPase activities were inhibited by amiodarone in a concentration dependent manner with IC 50 values of 50 μ M and 10 μ M respectively. [ 3 H]ouabain binding was also decreased in a concentration dependent manner with an IC 50 value of 12 μ M , and 50 μ M amiodarone totally inhibited [ 3 H]ouabain binding. Kinetics of [ 3 H]ouabain binding studies revealed that amiodarone inhibition of [ 3 H]ouabain binding is competitive. K + ‐activated p ‐nitrophenyl phosphatase activity showed a maximum inhibition of 32 per cent at 200 μ M amiodarone. Synaptosomal ATPase activities did not show any change in rats treated with amiodarone (20mg kg −1 day −1 ) for 6 weeks, when compared to controls. The treatment period may be short, since the reported neurological abnormalities in patients were observed during 3–5 years of treatment. The present results suggest that amiodarone induced neuropathy may be due to its interference with sodium dependent phosphorylation of Na + , K + ‐ATPase reaction, thereby affecting active ion transport phenomenon and oxidative phosphorylation resulting in low turnover of ATP in the nervous system.