Effects of non-narcotic analgesics and nonsteroid anti-inflammatory agents upon inorganic phosphates, intracellular potassium and impulse conduction in mammalian nerve fibers

Abstract

The effects of non-narcotic analgesics and of nonsteroid anti-inflammatory agents on the action potential and the content of intracellular potassium (K 1) and inorganic phosphate (P 1) were studied in the isolated cervical vagus nerve of the rabbit. Acetanilid, phenacetin and antipyrine in concentrations up to 10 mM showed no effect after incubations of 90 min at 37°. On the other hand, the anti-inflammatory agents, salicylic acid, phenylbutazone, oxyphenylbutazone, mefenamic, flufenamic and niflumic acid, in concentrations corresponding to the therapeutic level in human plasma during anti-rheumatic therapy, slowed nervous conduction and finally abolished excitability; this effect was accompanied by a loss of K 1 and an increase in P 1. Acetylsalicylic acid was ineffective at concentrations up to 5 mM, and abolished the action potential to 10 mM. Benzydamine, an anti-inflammatory agent without antirheumatic properties, abolished the action potential without elevation in P 1; barbituric acid, furosemide and the complexing agents, cysteamine, d-penicillamine and rubeanic acid, were ineffective. It is concluded that the abolition of excitability observed for the anti-inflammatory agents is due to the K 1 loss brought about by interference with oxydative phosphorylation. This effect does not appear to be due to their complexing action on metal ions.