Rojas-Corrales M O, Gibert-Rahola J, Micó J A
Department of Neuroscience, Faculty of Medicine, University of Cádiz, Spain.
Life Sci. 1998;63(12):PL175-80. doi: 10.1016/s0024-3205(98)00369-5.
Tramadol is a clinically-effective, centrally-acting analgesic. This drug is a racemic mixture of two enantiomers, each one displaying different mechanisms: (+)tramadol displays opioid agonist properties and inhibits serotonin reuptake while (-)tramadol inhibit preferentially noradrenaline reuptake. The action of tramadol on the monoaminergic reuptake is similar to that of antidepressant drugs. Therefore, we have examined the effects of (+/-)tramadol, (+)tramadol and (-)tramadol in a test predictive of antidepressant activity, the forced swimming test in mice. Both (+/-)tramadol and its (-) enantiomer displayed a dose-dependent reduction on immobility; while the effect induced by the (+) enantiomer was not significant. Inhibition of noradrenaline synthesis, but not of serotonin synthesis, was capable of blocking the effect of (+/-)tramadol. The alpha-adrenoceptor antagonist phentolamine, as well as the alpha2-adrenergic antagonist yohimbine, and the beta-adrenoceptor blocker propranolol countered the immobility-reducing action of (+/-)tramadol. Moreover, neither the serotoninergic blocker methysergide nor the opioid antagonist naloxone antagonized the effect of (+/-)tramadol. Our results show that (+/-)tramadol and (-)tramadol have antidepressant-like effect in mice, probably mediated by the noradrenergic system rather than the serotoninergic or opioidergic ones.
曲马多是一种临床有效的中枢性镇痛药。该药物是两种对映体的外消旋混合物，每种对映体表现出不同的作用机制：(+)曲马多具有阿片类激动剂特性并抑制5-羟色胺再摄取，而(-)曲马多则优先抑制去甲肾上腺素再摄取。曲马多对单胺能再摄取的作用与抗抑郁药物相似。因此，我们在一项预测抗抑郁活性的试验——小鼠强迫游泳试验中，研究了(±)曲马多、(+)曲马多和(-)曲马多的作用。(±)曲马多及其(-)对映体均呈现出剂量依赖性的不动时间减少；而(+)对映体诱导的效应不显著。抑制去甲肾上腺素合成而非5-羟色胺合成，能够阻断(±)曲马多的效应。α-肾上腺素能受体拮抗剂酚妥拉明、α2-肾上腺素能拮抗剂育亨宾以及β-肾上腺素能受体阻滞剂普萘洛尔，均可对抗(±)曲马多减少不动时间的作用。此外，5-羟色胺能阻滞剂甲基麦角新碱和阿片类拮抗剂纳洛酮均未拮抗(±)曲马多的效应。我们的结果表明，(±)曲马多和(-)曲马多在小鼠中具有类抗抑郁作用，可能是由去甲肾上腺素能系统介导，而非5-羟色胺能或阿片样物质能系统。
