Novel approach to demonstrate high efficacy of μ opioids in the rat vas deferens: A simple model of predictive value

P. Riba, Tamás Friedmann, Kornél P. Király, M. Al-Khrasani, Melinda Sobor, Muhammad F. Asim, Mariana Spetea, Helmut Schmidhammer, S. Fürst

Research output: Contribution to journalArticle

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Abstract

14-O-Methyloxymorphone and 14-methoxymetopon were reported as highly selective and potent μ opioid receptor agonists. The aim of this study was to demonstrate the opioid activity of these compounds in vitro and in vivo in comparison to oxymorphone, morphine and DAMGO. The μ opioid receptor efficacy, full or partial agonist nature of opioids was analyzed in the rat vas deferens (RVD) bioassay. Compared to oxymorphone, 14-O-methyloxymorphone and 14-methoxymetopon showed greater affinities to the rodent brain μ opioid receptors in receptor binding assays. In isolated organs 14-O-methyloxymorphone and 14-methoxymetopon were 3-10-fold more potent than the μ agonist opioid peptide, DAMGO. All tested compounds reached at least 70% maximum inhibition in mouse vas deferens (MVD) except morphine and oxymorphone. In the RVD, morphine could not exceed 50% inhibition of the twitches while 14-O-methyloxymorphone and 14-methoxymetopon showed inhibitory effects more than 70%. Oxymorphone reached only 4% maximal agonist effect and antagonized the inhibitory effect of DAMGO. The investigated morphinans produced dose-dependent antinociceptive activities in mice and rats. Both, 14-O-methyloxymorphone and 14-methoxymetopon are highly efficacious μ opioid receptor agonists in the RVD exhibiting full μ agonist properties. The RVD tissue contains μ receptors indicated by the comparable Ke values of the μ antagonist naltrexone against DAMGO in the MVD. RVD may be a good alternative to assess the μ receptor efficacy of opioid agonists providing a more physiological environment for the ligand-receptor interaction than other efficacy measuring methods such as the [35S]GTPγS binding assay.

Original languageEnglish
Pages (from-to)178-184
Number of pages7
JournalBrain Research Bulletin
Volume81
Issue number1
DOIs
Publication statusPublished - Jan 15 2010

Fingerprint

Vas Deferens
Opioid Analgesics
Oxymorphone
Ala(2)-MePhe(4)-Gly(5)-enkephalin
Opioid Receptors
Morphine
Morphinans
Naltrexone
Opioid Peptides
Biological Assay
Rodentia
14-methoxymetopon
14-O-methyloxymorphone
Ligands
Brain

Keywords

  • μ Opioid receptors
  • Antinociception
  • Efficacy
  • Morphinans
  • Mouse vas deferens
  • Rat vas deferens

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Novel approach to demonstrate high efficacy of μ opioids in the rat vas deferens : A simple model of predictive value. / Riba, P.; Friedmann, Tamás; Király, Kornél P.; Al-Khrasani, M.; Sobor, Melinda; Asim, Muhammad F.; Spetea, Mariana; Schmidhammer, Helmut; Fürst, S.

In: Brain Research Bulletin, Vol. 81, No. 1, 15.01.2010, p. 178-184.

Research output: Contribution to journalArticle

Riba, P. ; Friedmann, Tamás ; Király, Kornél P. ; Al-Khrasani, M. ; Sobor, Melinda ; Asim, Muhammad F. ; Spetea, Mariana ; Schmidhammer, Helmut ; Fürst, S. / Novel approach to demonstrate high efficacy of μ opioids in the rat vas deferens : A simple model of predictive value. In: Brain Research Bulletin. 2010 ; Vol. 81, No. 1. pp. 178-184.
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abstract = "14-O-Methyloxymorphone and 14-methoxymetopon were reported as highly selective and potent μ opioid receptor agonists. The aim of this study was to demonstrate the opioid activity of these compounds in vitro and in vivo in comparison to oxymorphone, morphine and DAMGO. The μ opioid receptor efficacy, full or partial agonist nature of opioids was analyzed in the rat vas deferens (RVD) bioassay. Compared to oxymorphone, 14-O-methyloxymorphone and 14-methoxymetopon showed greater affinities to the rodent brain μ opioid receptors in receptor binding assays. In isolated organs 14-O-methyloxymorphone and 14-methoxymetopon were 3-10-fold more potent than the μ agonist opioid peptide, DAMGO. All tested compounds reached at least 70{\%} maximum inhibition in mouse vas deferens (MVD) except morphine and oxymorphone. In the RVD, morphine could not exceed 50{\%} inhibition of the twitches while 14-O-methyloxymorphone and 14-methoxymetopon showed inhibitory effects more than 70{\%}. Oxymorphone reached only 4{\%} maximal agonist effect and antagonized the inhibitory effect of DAMGO. The investigated morphinans produced dose-dependent antinociceptive activities in mice and rats. Both, 14-O-methyloxymorphone and 14-methoxymetopon are highly efficacious μ opioid receptor agonists in the RVD exhibiting full μ agonist properties. The RVD tissue contains μ receptors indicated by the comparable Ke values of the μ antagonist naltrexone against DAMGO in the MVD. RVD may be a good alternative to assess the μ receptor efficacy of opioid agonists providing a more physiological environment for the ligand-receptor interaction than other efficacy measuring methods such as the [35S]GTPγS binding assay.",
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