Opiate receptor mediation of ketamine analgesia

Anesthesiology. 1982 Apr;56(4):291-7. 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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


  • Analgesics
  • Receptors, Opioid
  • Dextrorphan
  • Levorphanol
  • Etorphine
  • Ketamine