[Tifluadom, a benzodiazepine with opioid-like activity: study of its central mechanism of action in conscious dogs].

Abstract

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.

• Authors: M Schaal, E Freye, R Windelschmidt
• Journal: EEG-EMG Zeitschrift fur Elektroenzephalographie, Elektromyographie und verwandte Gebiete (EEG EMG Z Elektroenzephalogr Elektromyogr Verwandte Geb) Vol. 17 Issue 1 Pg. 27-31 (Mar 1986) ISSN: 0012-7590 [Print] Germany
• Vernacular Title: Tifluadom, ein Benzodiazepin mit opioidartigem Wirkcharakter: Eine Untersuchung zum zentralen Wirkmechanismus an wachen Hunden.
• PMID: 3084201 (Publication Type: English Abstract, Journal Article)

Chemical References

• Benzodiazepinones
• Benzomorphans
• Benzodiazepines
• Naloxone
• Flumazenil
• MR 2266
• tifluadom

Topics

• Animals
• Benzodiazepines (antagonists & inhibitors, pharmacology)
• Benzodiazepinones (pharmacology)
• Benzomorphans (pharmacology)
• Brain (drug effects)
• Dogs
• Dose-Response Relationship, Drug
• Electroencephalography
• Evoked Potentials, Somatosensory (drug effects)
• Flumazenil
• Naloxone (pharmacology)