Opiate receptor mediation of ketamine analgesia

• Published in: Anesthesiology (Philadelphia) Vol. 56; no. 4; pp. 291 - 297
• Main Authors: Finck, A D, Ngai, S H
• Format: Journal Article
• Language: English
• Published: United States 01-04-1982
• Subjects: Analgesics; Animals; Binding, Competitive; Brain - metabolism; Dextrorphan - metabolism; Etorphine - metabolism; Guinea Pigs; In Vitro Techniques; Ketamine - metabolism; Ketamine - pharmacology; Levorphanol - metabolism; Male; Mice; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Radioligand Assay; Rats; Rats, Inbred Strains; Receptors, Opioid - drug effects; Receptors, Opioid - metabolism; Stereoisomerism
• ISSN: 0003-3022
• DOI: 10.1097/00000542-198204000-00011

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.