Faden A I, Knoblach S, Mays C, Jacobs T P
Peptides. 1985;6 Suppl 1:15-7. doi: 10.1016/0196-9781(85)90006-3.
Naloxone, an opiate receptor antagonist, improves neurological outcome following traumatic cervical spinal cord injury in the cat and ischemic lumbar spinal cord injury in the rabbit. However, the doses of naloxone required have been quite high (greater than 1 mg/kg), suggesting that its beneficial actions are either not opiate receptor mediated or mediated by non-mu opiate receptors (which are less naloxone-sensitive). The kappa receptor appears to be the predominant opiate receptor in the spinal cord in a variety of species. For these reasons we evaluated the effects of a somewhat kappa selective opiate receptor antagonist WIN44,441-3 [WIN(-)] on neurological recovery following traumatic spinal injury in the cat and ischemic spinal injury in the rabbit. Animals treated with this more selective antagonist showed improved motor recovery as compared with animals treated with either physiological saline or with the dextroisomer of the WIN compound [WIN44,441-2; WIN(+)]. These findings support the hypothesis that motor dysfunction after spinal cord injury is in part mediated by opiate receptors and indicate that kappa selective opiate receptor antagonists may have particular therapeutic utility in spinal cord injury.
纳洛酮是一种阿片受体拮抗剂，可改善猫外伤性颈脊髓损伤和兔缺血性腰脊髓损伤后的神经功能转归。然而，所需的纳洛酮剂量相当高（大于1毫克/千克），这表明其有益作用要么不是由阿片受体介导的，要么是由对纳洛酮敏感性较低的非μ阿片受体介导的。κ受体似乎是多种物种脊髓中主要的阿片受体。基于这些原因，我们评估了一种对κ受体有一定选择性的阿片受体拮抗剂WIN44,441-3 [WIN(-)] 对猫外伤性脊髓损伤和兔缺血性脊髓损伤后神经功能恢复的影响。与用生理盐水或WIN化合物的右旋异构体 [WIN44,441-2；WIN(+)] 治疗的动物相比，用这种更具选择性的拮抗剂治疗的动物运动恢复情况有所改善。这些发现支持了脊髓损伤后运动功能障碍部分由阿片受体介导的假说，并表明κ受体选择性阿片受体拮抗剂在脊髓损伤中可能具有特殊的治疗作用。
