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INTRAVENOUS ANESTHESIA

14-Methoxymetopon, A Potent Opioid, Induces No Respiratory Depression, Less Sedation, and Less Bradycardia than Sufentanil in the Dog

Enno Freye, MD^*, Helmut Schmidhammer, PhD, and Leo Latasch, MD

*Clinics of Vascular Surgery and Renal Transplantation, University Clinics of Düsseldorf, Düsseldorf, Germany; Institute of Organic and Pharmaceutical Chemistry, University of Innsbruck, Innsbruck, Austria; and Department of Anesthesia, Nordwest Hospital, Frankfurt, Germany

Address correspondence and reprint requests to Enno Freye MD, Hamannstr. 37, 40882 Ratingen, Germany.

Abstract

Opioids of the µ-receptor type depress respiration and induce addiction. At 10-min intervals 14-methoxymetopon (HS-198), which is 20,000 times more potent than morphine in the acethylcholine-writhing test, was given in graded IV doses (3, 6, and 12 µg/kg) to awake, trained canines (n = 7). The following variables were derived: PaO₂, PaCO₂, heart rate (lead II of the electrocardiogram), mean arterial blood pressure, relative changes in the domain and the ß domain of the electroencephalogram, the somatosensory evoked potential, and the skin-twitch reflex to electrical stimuli. Thereafter, 20 µg/kg naltrexone was given for reversal. After a washout period, the same animals were exposed to similar doses of sufentanil (SUF) followed by naltrexone. Both opioids induced a dose-related bradycardia and hypotension. The maximal bradycardic effect was 19% after HS-198 and 42% after SUF (P < 0.005). The maximal hypotension was 6% after HS-198 and 20% after SUF (P < 0.01). In the electroencephalogram, power in the band increased by 288% after HS-198 and by 439% after SUF (P < 0.01); simultaneously, power in the ß 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 increased by 56.8% and 6.6% in SUF and HS-198, respectively (P < 0.001). Both opioids 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 changes back to control. Compared with SUF, HS-198 does not induce hypoxia and hypercarbia, induces less hypotension and bradycardia, and induces less sedative effects.

Implications: Compared with sufentanil, 14-methoxymetopone does not induce hypoxia and hypercarbia, induces less hypotension and bradycardia, and induces less sedative effects (electroencephalogram). Antinociception is similar to sufentanil (skin-twitch method, amplitude depression in the evoked potential). All effects are reversed by naltrexone. Interaction of -receptor is suggested.

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				L. Mahurter, C. Garceau, J. Marino, H. Schmidhammer, G. Toth, and G. W. Pasternak Separation of Binding Affinity and Intrinsic Activity of the Potent {micro}-Opioid 14-Methoxymetopon J. Pharmacol. Exp. Ther., October 1, 2006; 319(1): 247 - 253. [Abstract] [Full Text] [PDF]