Smith D J, Bouchal R L, deSanctis C A, Monroe P J, Amedro J B, Perrotti J M, Crisp T
Department of Anesthesiology, West Virginia University Medical Center, Morgantown 26506.
Neuropharmacology. 1987 Sep;26(9):1253-60. doi: 10.1016/0028-3908(87)90084-0.
Analgesia induced by ketamine appears to be partially mediated by opiate mechanisms. Not only is its action attenuated by the narcotic antagonist naloxone, but the drug has a weak affinity for, and interacts stereoselectively at, opiate receptors. It also produces a classical narcotic action on the guinea-pig ileum. The present study showed that analgesic doses of the drug in rats yielded concentrations sufficient to interact effectively at opiate binding sites in vivo. A dose-dependent (80-120 mg/kg i.p.) inhibition of the binding of [3H]naloxone was observed in both brain and spinal cord. All regions of the brain (except the cerebellum) were affected, but the reduction was significant in the cortex, hippocampus, thalamus and striatum. Thus, a component of ketamine-induced analgesia could be related to a functional interaction with opiate receptors. Additionally, ketamine may be similar to morphine in its preference for the mu, rather than the delta sub-type of opiate receptors, and thus may promote mu-mediated pharmacological effects. For example, in vitro studies of radioligand binding showed that ketamine and morphine were four times more effective in inhibiting the binding of [3H]dihydromorphine than that of [3H] [D-Ala2, D-Leu5] enkephalin. On the other hand, ketamine also effectively interacted at a component of the sigma opiate/phencyclidine binding sites that appears to be relatively insensitive to morphine. This component may be involved in dysphoria induced by ketamine.
氯胺酮诱导的镇痛作用似乎部分由阿片类机制介导。其作用不仅会被麻醉拮抗剂纳洛酮减弱，而且该药物对阿片受体具有弱亲和力，并能在阿片受体上进行立体选择性相互作用。它还对豚鼠回肠产生典型的麻醉作用。本研究表明，给大鼠使用镇痛剂量的该药物后，其体内浓度足以在阿片结合位点进行有效相互作用。在脑和脊髓中均观察到剂量依赖性（80 - 120毫克/千克腹腔注射）的[³H]纳洛酮结合抑制。大脑的所有区域（除小脑外）均受影响，但在皮质、海马体、丘脑和纹状体中这种减少具有显著性。因此，氯胺酮诱导的镇痛作用的一个组成部分可能与和阿片受体的功能性相互作用有关。此外，氯胺酮在对阿片受体μ亚型而非δ亚型的偏好上可能与吗啡相似，因此可能促进μ介导的药理作用。例如，放射性配体结合的体外研究表明，氯胺酮和吗啡在抑制[³H]二氢吗啡结合方面比抑制[³H][D - Ala², D - Leu⁵]脑啡肽结合有效四倍。另一方面，氯胺酮也能在似乎对吗啡相对不敏感的σ阿片/苯环己哌啶结合位点的一个组分上有效相互作用。该组分可能与氯胺酮诱导的烦躁不安有关。
