title: Opiate receptor mediation of ketamine analgesia.
abstract: Previous workers have noted that analgesia produced by ketamine can be antagonized by the narcotic antagonist, naloxone. In order to elaborate further the apparent similarity between ketamine- and narcotic-induced analgesia, the authors examined the effects of ketamine in three standard test systems for the opiate receptor. In a radioligand binding assay using 3H-dihydromorphine, ketamine stereospecifically bound to opiate receptors in rat brain homogenate, (+) ketamine being 2-3 times more potent than the (-) enantiomer of ketamine. In a bioassay for the opiate receptor, using the longitudinal muscle-myenteric plexus of the guinea pig ileum, ketamine inhibited the twitch-like muscular contractions, as do narcotics. However, only the inhibitory effects of (+) ketamine, which in this system also was twice as potent as (-) ketamine, could be partially antagonized by naloxone, suggesting that this enantiomer is responsible for the opiate receptor-related effects of ketamine. In vivo, the authors found that ketamine displaces 3H-etorphine, a potent narcotic, from opiate receptors in regional areas of the mouse brain, especially in the thalamic region, but not in the cortex. The results suggest that a significant mechanism of ketamine-induced analgesia is mediated by opiate receptors.
mesh_terms: D000700:Analgesics; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D003917:Dextrorphan / Q000378:metabolism; D005048:Etorphine / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007649:Ketamine / Q000378:metabolism / Q000494:pharmacology*; D007981:Levorphanol / Q000378:metabolism; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D000700:Analgesics; D011957:Receptors, Opioid; D003917:Dextrorphan; D007981:Levorphanol; D005048:Etorphine; D007649:Ketamine