Highly potent novel opioid receptor agonist in the 14-alkoxymetopon series.

@article{Frst1993HighlyPN,
  title={Highly potent novel opioid receptor agonist in the 14-alkoxymetopon series.},
  author={Zsuzsanna F{\"u}rst and Be{\'a}ta B{\'u}z{\'a}s and Tam{\'a}s Friedmann and Helmut Schmidhammer and Anna Borsodi},
  journal={European journal of pharmacology},
  year={1993},
  volume={236 2},
  pages={
          209-15
        }
}
The newly synthesized 14-alkoxymetopon derivatives, 14-methoxymetopon, 14-ethoxymetopon, 14-methoxy-5-methyl-morphinone, exhibit high affinity for the naloxone binding sites in rat brain. A substantial decrease in affinity was observed, in the presence of NaCl indicating a high degree of agonist activity. All three 14-alkoxymetopon derivatives displayed high affinity for [3H][D-Ala2,(Me)Phe4,Gly-ol5]enkephalin ([3H]DAMGO) binding sites, much less potency toward delta sites and were the least… Expand
In vitro opioid activity profiles of 6-amino acid substituted derivatives of 14-O-methyloxymorphone.
TLDR
The newly developed ionizable derivatives of the highly potent opioid analgesic 14-O-methyloxymorphone could find clinical applications as potent analgesics without the adverse actions of centrally acting opioids. Expand
Synthesis and Pharmacological Activities of 6-Glycine Substituted 14-Phenylpropoxymorphinans, a Novel Class of Opioids with High Opioid Receptor Affinities and Antinociceptive Potencies†
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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. Expand
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The most striking finding of this study is that the derivatives from the novel series of N-methyl-14-phenylpropoxymorphinans acted as extremely powerful antinociceptive with potencies higher than that of 14-methoxymetopon and even etorphine. Expand
Signal transduction efficacy of the highly potent mu opioid agonist 14-methoxymetopon.
TLDR
The efficacy (tau) and apparent in vivo affinity (KA) of the high-potency alkoxymorphinan 14-methoxymetopon, as previously determined in radioligand binding assays - was determined and was confirmed in the present behavioral tests of thermal antinociception. Expand
Separation of Binding Affinity and Intrinsic Activity of the Potent μ-Opioid 14-Methoxymetopon
TLDR
14-methoxymetopon is a potent agonist against all of the mMOR-1 splice variants, but its potency ranged widely despite similar binding affinities for most of the variants and may give insight into its unusual pharmacological profile. Expand
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TLDR
Findings provide further evidence that the nature of the substituent at position 14 has a major impact on the abilities of morphinan-6-one derivatives to interact with opioid receptors. Expand
A novel µ-opioid receptor ligand with high in vitro and in vivo agonist efficacy.
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TLDR
It is demonstrated that 14-methoxymetopon is a highly potent mu-opioid with a pharmacological profile distinct from that of the traditional mu-OPioid morphine. Expand
In vitro and in vivo pharmacological profile of the 5-benzyl analogue of 14-methoxymetopon, a novel μ opioid analgesic with reduced propensity to alter motor function
TLDR
The 5-benzyl analogue of 14-MM emerged as a novel potent μ opioid antinociceptive agent with reduced propensity to cause unwanted motor impairment. Expand
14-Phenylpropyloxymorphinan-6-ones with Unanticipated Agonist Properties: Extending the Scope of Common Structure-Activity Relationships
The synthesis, biological, and pharmacological evaluations of 14‚-O-phenylpropyl-substituted morphinan-6-ones are described. The most striking finding of this study was that all of the compounds fromExpand
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