Analgesic activity and toxicity of potent analgesics, ohmefentanyl and mefentanyl

The analgesic potency and the duration of ohmefentanyl {N-[1-(2-hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide, OMF}, mefentanyl {N-[1-(2-phenylethyl)-3-methyl-4-poperidyl]-N-phenylpropanamide,MF}, fentanyl (F) and morphine (M) were determined by 4 methods(mice, ip, hot plate; mice, sc, writhing body; rats, sc, tail flick; and rabbits, iv, K+ permeation). The analgesic potency: OMF>MF>F>M. In mice hot plate test, ip analgesic ED50 of OMF was 1.51 μg/kg, its analgesic activity was 25.8 times as potent as that of F or 7880 times as potent as that of M, and its duration of analgesic action was 6.6 times longer than that of F or similar to that of M. After iv analgesic 2×ED50 in rabbits, the respiratory depression by OMF and MF was less than that by F. No significant changes in EEG, ECG and BP were found. The therapeutic indices (LD50/ED50) of OMF and MF were 5562 and 1159 in mice, and 61.0 and 29.3 in rabbits, respectively. The toxic responses of OMF and MF on rabbits were effectively antagonized by nalorphine.