Kayser V, Fournie-Zaluski M C, Guilbaud G, Roques B P
Unité de Recherches de Physiopharmacologie du Système Nerveux, U 161 INSERM, Paris, France.
Brain Res. 1989 Sep 11;497(1):94-101. doi: 10.1016/0006-8993(89)90974-8.
The effects of various i.v. doses (2.5, 5, 10 and 15 mg/kg) of the highly efficient inhibitor of multiple enkephalin-degrading enzymes, Kelatorphan, were evaluated on the vocalization threshold to paw pressure in normal rats and in rats with Freund's adjuvant-induced arthritis. In normal rats, Kelatorphan at doses as low as 2.5 mg/kg i.v. at which the enkephalinase inhibitor acetorphan was ineffective, produced potent antinociceptive effects, comparable to that induced by 1 mg/kg i.v. morphine. In contrast, for the higher doses used (5, 10, 15 mg/kg i.v.), the effects of Kelatorphan were not more pronounced than that of acetorphan. Unlike acetorphan, Kelatorphan was found to be much more effective in arthritic than in normal rats in raising the vocalization threshold, even at the lower concentration, 2.5 mg/kg i.v.: 244% in arthritic vs 144% in normal rats. The effects of Kelatorphan were prevented by naloxone at the dose of 0.5 mg/kg i.v. The enhanced potency of Kelatorphan is discussed in relation with the increase in peptidase-sensitive dynorphin fragments in arthritic rats.
评估了高效多脑啡肽降解酶抑制剂凯拉托芬（Kelatorphan）不同静脉注射剂量（2.5、5、10和15毫克/千克）对正常大鼠和弗氏佐剂诱导性关节炎大鼠爪部压力发声阈值的影响。在正常大鼠中，静脉注射低至2.5毫克/千克剂量的凯拉托芬即可产生强效的镇痛作用，该剂量下脑啡肽酶抑制剂醋托芬（acetorphan）无效，其镇痛效果与静脉注射1毫克/千克吗啡相当。相比之下，对于更高的使用剂量（静脉注射5、10、15毫克/千克），凯拉托芬的效果并不比醋托芬更显著。与醋托芬不同，即使在较低浓度（静脉注射2.5毫克/千克）下，凯拉托芬提高发声阈值的效果在关节炎大鼠中也比正常大鼠更为有效：关节炎大鼠中提高了244%，而正常大鼠中提高了144%。静脉注射0.5毫克/千克剂量的纳洛酮可阻断凯拉托芬的作用。结合关节炎大鼠中对肽酶敏感的强啡肽片段增加的情况，对凯拉托芬增强的效力进行了讨论。
