Iorio L C, Latranyi M, Heath E, Barnett A
J Pharmacol Exp Ther. 1980 Jun;213(3):445-9.
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.
在酵母致爪试验中，非麻醉性镇痛药氯尼辛、氟尼辛、乙酰水杨酸、氨基比林和保泰松的抗伤害感受作用被L-赖氨酸阻断。阻断发生在不影响痛阈的L-赖氨酸剂量下。阻断作用的位点或机制尚不能确定。由于给药后长达2小时氟尼辛的血浆或脑水平未改变且氟尼辛与血浆蛋白的结合未受影响，L-赖氨酸似乎不太可能阻止镇痛药到达活性位点。L-赖氨酸的阻断作用似乎至少部分发生在外周部位，因为它未被L-精氨酸或L-鸟氨酸阻断，L-精氨酸和L-鸟氨酸与L-赖氨酸竞争共同转运系统，因此，如果L-赖氨酸的作用是中枢性的，它们会降低L-赖氨酸的作用。然而，不能排除中枢神经系统内的阻断作用。L-赖氨酸的拮抗作用似乎不涉及内源性5-羟色胺，因为它未被5-羟色胺前体5-羟色氨酸或5-羟色胺摄取特异性阻断剂氟西汀逆转。与非麻醉性镇痛药的阻断作用相反，L-赖氨酸增强了吗啡的抗伤害感受作用。
