Binding characteristics of [3H]14-methoxymetopon, a high affinity mu-opioid receptor agonist.

Mariana Spetea, Fanni Tóth, Johannes Schütz, Ferenc Otvös, Géza Tóth, S. Benyhe, A. Borsodi, Helmut Schmidhammer

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The highly potent micro -opioid receptor agonist 14-methoxymetopon (4,5alpha-epoxy-3-hydroxy-14beta-methoxy-5beta,17-dimethylmorphinan-6-one) was prepared in tritium labelled form by a catalytic dehalogenation method resulting in a specific radioactivity of 15.9 Ci/mmol. Opioid binding characteristics of [3H]14-methoxymetopon were determined using radioligand binding assay in rat brain membranes. [3H]14-Methoxymetopon specifically labelled a single class of opioid sites with affinity in low subnanomolar range (Ki = 0.43 nm) and maximal number of binding sites of 314 fmol/mg protein. Binding of [3H]14-methoxymetopon was inhibited by ligands selective for the micro -opioid receptor with high potency, while selective kappa-opioids and delta-opioids were weaker inhibitors. 14-Methoxymetopon increased guanosine-5'-O-(3-[35S]thio)-triphosphate ([35S]GTPgammaS) binding with an EC50 of 70.9 nm, thus, providing evidence for the agonist character of this ligand. The increase of [35S]GTPgammaS binding was inhibited by naloxone and selective micro -opioid antagonists, indicating a micro -opioid receptor-mediated action. [3H]14-Methoxymetopon is one of the few nonpeptide mu-opioid receptor agonists available in radiolabelled form up to now. Due to its high affinity and selectivity, high stability and extremely low nonspecific binding (

Original languageEnglish
Pages (from-to)290-295
Number of pages6
JournalEuropean Journal of Neuroscience
Volume18
Issue number2
Publication statusPublished - Jul 2003

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mu Opioid Receptor
Guanosine 5'-O-(3-Thiotriphosphate)
Opioid Analgesics
Opioid Receptors
Ligands
Radioligand Assay
Narcotic Antagonists
Tritium
Naloxone
Radioactivity
Binding Sites
Membranes
Brain
14-methoxymetopon
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Spetea, M., Tóth, F., Schütz, J., Otvös, F., Tóth, G., Benyhe, S., ... Schmidhammer, H. (2003). Binding characteristics of [3H]14-methoxymetopon, a high affinity mu-opioid receptor agonist. European Journal of Neuroscience, 18(2), 290-295.

Binding characteristics of [3H]14-methoxymetopon, a high affinity mu-opioid receptor agonist. / Spetea, Mariana; Tóth, Fanni; Schütz, Johannes; Otvös, Ferenc; Tóth, Géza; Benyhe, S.; Borsodi, A.; Schmidhammer, Helmut.

In: European Journal of Neuroscience, Vol. 18, No. 2, 07.2003, p. 290-295.

Research output: Contribution to journalArticle

Spetea, M, Tóth, F, Schütz, J, Otvös, F, Tóth, G, Benyhe, S, Borsodi, A & Schmidhammer, H 2003, 'Binding characteristics of [3H]14-methoxymetopon, a high affinity mu-opioid receptor agonist.', European Journal of Neuroscience, vol. 18, no. 2, pp. 290-295.
Spetea, Mariana ; Tóth, Fanni ; Schütz, Johannes ; Otvös, Ferenc ; Tóth, Géza ; Benyhe, S. ; Borsodi, A. ; Schmidhammer, Helmut. / Binding characteristics of [3H]14-methoxymetopon, a high affinity mu-opioid receptor agonist. In: European Journal of Neuroscience. 2003 ; Vol. 18, No. 2. pp. 290-295.
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