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

@article{Freye200014MethoxymetoponAP,
  title={14-Methoxymetopon, A Potent Opioid, Induces No Respiratory Depression, Less Sedation, and Less Bradycardia than Sufentanil in the Dog},
  author={Enno Christian Kurt Freye and Helmut Schmidhammer and Leo Latasch},
  journal={Anesthesia \& Analgesia},
  year={2000},
  volume={90},
  pages={1359–1364}
}
Opioids of the &mgr;-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 &mgr;g/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 &dgr; domain and the &bgr; domain of the… 
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Replacement of the 14-methoxy group with a phenylpropoxy group led to an enhancement in affinity to all three opioid receptor types, with most pronounced increases in δ and κ activities, hence resulting in a loss of μ receptor selectivity.
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Recent advances in chemistry, ligand-based structure activity relationships and pharmacology of 14-alkoxymorphinans are reviewed in this chapter and their potential therapeutic opportunities are summarized.
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