title: Opioid receptors-mediated respiratory effects and antinociception after S(+)-ketamine.
abstract: Until recently only the racemic mixture of ketamine was available for anesthesia. Little is known, of the central nervous effects of the pharmacological more potent S(+)-isomer. In order to evaluate the effects on respiration, the electroencephalographic activity and on the somatosensory evoked potential (SEP), increasing doses of S(+)-ketamine (2-5-10-20 mg/kg) were given to trained and awake canines (n = 10) at 10 minutes interval. To demask any opioid-receptor mediated effect, the highly selective mu-antagonist naltrexone or the highly selective delta-antagonist naltrindole (NTI) was given after S(+)-ketamine. S(+)-ketamine depressed respiration in a dose-related manner (PaO2 decrease, PaCO2 increase). Hypoxia was fully reversed by NTI and naltrexone; however hypercapnia was only partly reversed. S(+)-ketamine induced a dose-related increase of power in the theta-band (3-8 Hz) with little increase of power in the alpha-domain (8-13 Hz). Both these changes were reversed by NTI and naltrexone. Compared to control, low doses (2-5 mg/kg) increased power (p < 0.05) in the beta-(13-30 Hz) and decreased power (p < 0.05) in the delta-(0.5-3 Hz) band. These effects changed with higher doses (5-10 mg/kg). When compared to control, power in the delta-domain was significantly higher (p < 0.05), while power in the beta-band decreased significantly following 20 mg/kg of S(+)-ketamine. NTI was capable to reverse all these effects, however, naltrexone was not. In the SEP, S(+)-ketamine induced a dose-related increase in peak latency and a depression of amplitude of more than 50% when compared to control. Latency changes and amplitude height was only partly restored by both antagonists. The present results corroborate the connotation, that the central effects of the S(+)-isomer of ketamine are related to the opioid delta- and mu-receptor. The respiratory depression may be of importance when S(+)-ketamine is used (in very high doses). The S(+)-isomer induced hypersynchronisation in the EEG, suggests a deep plane of anesthesia; the pronounced blockade of nociceptive stimuli in the sensory nervous pathways suggests an analgesic effect which is partly mediated by the opioid receptor.
authors.affiliation: Department of Anesthesiology, Krankenhaus Nordwest, Frankfurt/M, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Latasch
authors.forename: E
authors.initials: E
authors.lastname: Freye
mesh_terms: D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D011957:Receptors, Opioid / Q000378:metabolism*; D012119:Respiration / Q000187:drug effects*; D013237:Stereoisomerism; D014851:Wakefulness / Q000187:drug effects
chemical_list: D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009271:Naltrexone; D007649:Ketamine; C055382:naltrindole