Receptor binding, analgesic and antitussive potency of tramadol and other selected opioids.
Receptor binding, analgesic and antitussive potency of tramadol and other selected opioids.
复制标题
曲马多和其他选定阿片类药物的受体结合、镇痛和镇咳功效。
DOI：
--
复制
发表时间：
1988
期刊：
影响因子：
--
通讯作者：
J. Schneider
中科院分区：
文献类型：
--
作者：
Hennies Hh;E. Friderichs;J. Schneider
研究了以甲氧基取代酚羟基对吗啡-可待因、氢吗啡酮-氢可酮和o -去甲基曲马多(l235)-曲马多相应偶对阿片受体结合、镇痛和止咳作用的影响。研究了放射性配体二氢吗啡（μ -位点）、乙基酮环唑嗪（k-位点）、d - ala2 - d - leu5 -脑啡肽（δ -位点）和纳洛酮（无选择性结合）在大鼠全脑膜（不含小脑）上的结合。观察大鼠的镇痛作用（甩尾）和止咳作用（氨蒸汽致咳），并计算给药后10 min的ED50值，比较疗效。所有游离羟基化合物都比相应的甲氧基衍生物具有更高的阿片受体亲和力，并且在mu位点上更活跃。甲氧基衍生物可待因和曲马多仅对mu-、kappa-或delta结合具有低亲和力，缺乏选择性。而氢可酮则表现出较强的低选择性结合。羟基化合物比甲氧基同系物具有更高的镇痛活性，镇痛似乎与mu结合亲和力有关。可待因和氢可酮的止咳作用弱于相应的羟基化合物，而o -去甲基曲马多和曲马多之间无显著差异。只有在曲马多组中，甲氧基替代增加了与镇痛效力相关的止咳效力。
The influence of replacing the phenolic hydroxyl by the methoxy group on opioid receptor binding, analgesic and antitussive action was investigated in the corresponding couples morphine-codeine, hydromorphone-hydrocodone and O-desmethyltramadol (L 235)-tramadol. Binding was studied on rat whole brain membranes (without cerebellum) with the radioligands dihydromorphine (mu-site), ethylketocyclazocine (k-site), D-Ala2-D-Leu5-enkephalin (delta-site) and naloxone (no selective binding). Analgesia (tail flick) and antitussive action (NH3-vapour induced cough) was investigated in rats and ED50 values 10 min after i.v. application were calculated to compare efficacy. All free hydroxyl compounds had higher opioid receptor affinities than the corresponding methoxy derivatives and were more active at the mu-site. The methoxy derivatives codeine and tramadol only had low affinities lacking selectivity towards mu-, kappa-, or delta-binding. Hydrocodone in contrast showed strong and mu-selective binding. The hydroxy compounds had higher analgesic activity than the methoxy congeners and analgesia appeared to correlate with mu-binding affinity. Codeine and hydrocodone were weaker antitussives than the corresponding hydroxy compounds, whereas no significant difference was found between O-desmethyltramadol and tramadol. Only in the tramadol group the methoxy substitution increased antitussive potency in relation to analgesic potency.