Advokat C, Rhein F Q
Department of Psychology, Louisiana State University, Baton Rouge 70803, USA.
Brain Res. 1995 Nov 13;699(1):157-60. doi: 10.1016/0006-8993(95)01023-o.
Neurophysiologic and behavioral evidence indicates that excitatory amino acid (EAA) antagonists may provide a new class of selective analgesics for opiate resistant, neuropathic pain syndromes. Therapeutic applications have been limited because of unacceptable side effects of most EAA blockers. However, dextrorphan, a metabolite of the antitussive drug, dextromethorphan, is a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) subtype of EAA receptor with few side effects and a moderate analgesic effect in animals with peripheral neuropathy. It may therefore, have clinical benefit, either alone or in combination with opiates, for neuropathic pain. In this study a subeffective dose of dextrorphan (15 mg/kg) was combined with several doses of morphine (1.5, 3.0 and 6.0 mg/kg) and assessed in an animal model of central injury, the tail flick response of the acute spinal rat. At doses which were individually ineffective, the combination of dextrorphan and morphine (15 and 1.5 mg/kg, respectively) produced a significant antinociceptive response. The same dose of dextrorphan also increased the antinociceptive response to 3.0 and 6.0 mg/kg of morphine. Coadministration of low doses of an NMDA antagonist and an opiate, might have clinical benefit for the relief of pain with reduced risk of undesirable side effects.
神经生理学和行为学证据表明，兴奋性氨基酸（EAA）拮抗剂可能为对阿片类药物耐受的神经性疼痛综合征提供一类新的选择性镇痛药。由于大多数EAA阻滞剂存在不可接受的副作用，其治疗应用受到限制。然而，右啡烷是镇咳药右美沙芬的一种代谢产物，是EAA受体N-甲基-D-天冬氨酸（NMDA）亚型的非竞争性拮抗剂，副作用少，对周围神经病变动物有中等程度的镇痛作用。因此，它单独或与阿片类药物联合使用可能对神经性疼痛有临床益处。在本研究中，将亚有效剂量的右啡烷（15mg/kg）与几种剂量的吗啡（1.5、3.0和6.0mg/kg）联合使用，并在中枢损伤的动物模型——急性脊髓大鼠甩尾反应中进行评估。在单独使用无效的剂量下，右啡烷和吗啡（分别为15和1.5mg/kg）的组合产生了显著的抗伤害感受反应。相同剂量的右啡烷还增强了对3.0和6.0mg/kg吗啡的抗伤害感受反应。联合使用低剂量的NMDA拮抗剂和阿片类药物可能对缓解疼痛有临床益处，同时降低出现不良副作用的风险。
