Klepstad P, Maurset A, Moberg E R, Oye I
Department of Pharmacology, Oslo University School of Medicine, Norway.
Eur J Pharmacol. 1990 Oct 23;187(3):513-8. doi: 10.1016/0014-2999(90)90379-k.
Both chiral forms of ketamine caused analgesia when administered in subanesthetic doses to human volunteers suffering acute, experimentally induced ischemic pain. S-Ketamine was 4 times more potent than R-ketamine as an analgesic agent in this model system. The relative order of analgesic potency of the two enantiomers was compared to their relative affinity for phencyclidine (PCP) binding sites (associated with the NMDA receptor-operated ion channel) and for sigma binding sites (which are not associated with the NMDA receptor complex). The relative analgesic potency of the enantiomers correlated positively with their relative affinity for PCP sites and negatively with their relative affinity for sigma sites. The results strongly indicate that PCP sites, but not sigma sites, are functional receptors mediating the analgesic effect of ketamine. This is consistent with the hypothesis that NMDA receptors are essential for pain perception in humans. Disturbances of other sensory modalities, in particular somatosensory perception, vision and hearing, were the main side-effects observed. These effects were qualitatively similar for both enantiomers and were closely associated with their analgesic action. The NMDA type of excitatory amino acid receptor thus appears to be widely involved in the processing of sensory afferent signals in the human brain.
当以亚麻醉剂量给遭受急性实验性诱导缺血性疼痛的人类志愿者使用时，氯胺酮的两种手性形式均产生了镇痛作用。在该模型系统中，S-氯胺酮作为镇痛剂的效力是R-氯胺酮的4倍。将两种对映体的镇痛效力相对顺序与其对苯环己哌啶（PCP）结合位点（与NMDA受体操纵的离子通道相关）和对σ结合位点（与NMDA受体复合物无关）的相对亲和力进行了比较。对映体的相对镇痛效力与其对PCP位点的相对亲和力呈正相关，与其对σ位点的相对亲和力呈负相关。结果强烈表明，PCP位点而非σ位点是介导氯胺酮镇痛作用的功能性受体。这与NMDA受体对人类疼痛感知至关重要的假设是一致的。观察到的主要副作用是其他感觉模式的紊乱，尤其是躯体感觉、视觉和听觉。两种对映体的这些效应在性质上相似，且与它们的镇痛作用密切相关。因此，NMDA型兴奋性氨基酸受体似乎广泛参与了人类大脑中感觉传入信号的处理。
