Blockade by l-lysine of non-narcotic analgesics

The antinociceptive effects of the non-narcotic analgesics clonixin, flunixin, acetylsalicylic acid, aminopyrine and phenylbutazone in the yeast paw test were blocked by l-lysine. Blockade occurred at doses of l-lysine which did not affect pain threshold. The site(s) or mechanism of action of blockade could not be determined with certainty. It appears unlikely that l-lysine prevented the analgesics from getting to active sites since plasma or brain levels of flunixin were not altered for up to 2 hr after drug administration and binding of flunixin to plasma protein was not affected. Blockade by l-lysine appears to occur at least in part at a peripheral site since it was not blockade by l-arginine or l-ornithine which compete for a common transport system with l-lysine and, hence, would have reduced the effect of l-lysine if its actions were central. However, blockade within the central nervous system cannot be ruled out. Antagonism by l-lysine does not seem to involve endogenous serotonin since it was not reversed by the serotonin precursor, 5-hydroxytryptophan, or by fluoxetine, a specific blocker of serotonin uptake. In contrast to the block of non-narcotic analgesics, l-lysine potentiated the antinociceptive effects of morphine.