Quantitative electroencephalographic and metabolic studies of midaflur, a new anesthetic agent

Midaflur [4-amino-2,2,5,5-tetrakis(trifluoro methyl)-3-imidazoline] was tested for its ability to induce changes in (i) the EEG of Sprague-Dawley rats with chronically implanted electrodes and (ii) metabolic and kidney functions on Fischer 344 rats. Ataxia and loss of righting reflex were observed in animals given the smaller doses (2 to 5 mg/kg of body weight, intraperitoneally), with little or no effect on the EEG. At higher dose rates, a significant linear dose-response relationship was found for midaflur in depressing brain activity. Changes in body weight and feed and water intake occurred in rats given single doses of midaflur (2 to 20 mg/kg). These effects seemed to be due, in part, to the drug-induced inactivity and to the vehicle in which midaflur has been formulated (equal parts of ethyl alcohol, propylene glycol, and water). Urinary volumes were reduced after injection of midaflur, possibly as a consequence of the changes in water intake. Since midaflur is highly fluorinated, studies were done to detect possible release of inorganic fluoride due to metabolic breakdown. Serum fluoride concentrations in rats given single doses of midaflur (2 to 20 mg/kg) were consistently lower than those of control (untreated) animals, reflecting a reduction in the daily intake of fluoride as a consequence of the diminished feed intake. Significant changes were not observed in the urinary fluoride concentrations in treated rats as compared with these values in control animals given the vehicle alone.