[Tifluadom, a benzodiazepine with opioid-like activity: study of its central mechanism of action in conscious dogs].
A derivative of the 1,4-benzodiazepine series with reported opioid activity was evaluated in regard to its effect on central nervous activity in the awake canine. Additionally a possible benzodiazepine- or opioid-receptor interaction was evaluated by using specific antagonists. In 10 experiments increasing doses of tifluadom (5, 10, 20, 40, 80 micrograms/kg) modified somato-sensory-evoked potentials (SEP) inducing a dose-related latency change (40-80 micrograms/kg) and a suppression (80 micrograms/kg) of the P50-peak. Both effects are interpreted as a modification of stimuli reaching the somatosensory cortex. EEG-spectral analysis was characterized by a dose-related decrease of power in the higher frequency range (13-40 Hz) accompanied by an increase of power in the lower band (0.5-3.5 Hz). This effect was paralleled by deep sedation. The specific benzodiazepine antagonist Ro 15-1788 (240 micrograms/kg) was ineffective in reversing central nervous EEG- and SEP-changes. Naloxone (20 micrograms/kg) induced a short-term (5 min) arousal and a partial reversal of SEP-changes. The specific opioid-kappa-antagonist Mr 2266 (20 micrograms/kg) however, induced a long lasting return of power spectra and SEP-changes back to control. This results suggest that tifluadom, although being structurally a benzodiazepine, interacts with an opioid sub-receptor of the kappa-type, which is known to induce sedation and supraspinal analgesia without respiratory depression.
D000818:Animals; D001569:Benzodiazepines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology; D001575:Benzomorphans / Q000494:pharmacology; D001921:Brain / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D005442:Flumazenil; D009270:Naloxone / Q000494:pharmacology
D001570:Benzodiazepinones; D001575:Benzomorphans; D001569:Benzodiazepines; D009270:Naloxone; D005442:Flumazenil; C027247:MR 2266; C035470:tifluadom
Tifluadom, ein Benzodiazepin mit opioidartigem Wirkcharakter: Eine Untersuchung zum zentralen Wirkmechanismus an wachen Hunden.