14-methoxymetopon, a potent opioid, induces no respiratory depression, less sedation, and less bradycardia than sufentanil in the dog

Opioids of the mu-receptor type depress respiration and induce addiction. A t 10-min intervals 14-methoxymetopon (HS-198), which is 20,000 times more p otent than morphine in the acethylcholine-writhing test, was given in grade d IV doses (3, 6, and 12 mu g/kg) to awake, trained canines (n = 7). The fo llowing variables were derived: PaO2, PaCO2, heart rate (lead II of the ele ctrocardiogram), mean arterial blood pressure, relative changes in the delt a domain and the beta domain of the electroencephalogram, the somatosensory evoked potential, and the skin-twitch reflex to electrical stimuli. Therea fter, 20 mu g/kg naltrexone was given for reversal. After a washout period, the same animals were exposed to similar doses of sufentanil (SUF) followe d by naltrexone. Both opioids induced a dose-related bradycardia and hypote nsion. The maximal bradycardic effect was 19% after HS-198 and 42% after SU F (P < 0.005). The maximal hypotension was 6% after HS-198 and 20% after SU F (P < 0.01). In the electroencephalogram, power in the delta band increase d by 288% after HS-198 and by 439% after SUF (P < 0.01); simultaneously, po wer in the beta band decreased by 71% and by 95.7%, respectively (P < 0.01) . PaO2 decreased by 41% after SUF and by 4% after HS-198, and PaCO2 increas ed by 56.8% and 6.6% in SUF and HS-198, respectively (P < 0.001). Both opio ids induced a dose-related depression in the somatosensory evoked potential and increased tolerance to skin-twitch. The maximal effect was 92.7% after SUF and 81.3% after HS-198 was not significant. Naltrexone reversed all ch anges back to control. Compared with SUF, HS-198 does not induce hypoxia an d hypercarbia, induces less hypotension and bradycardia, and induces less s edative effects.