Affinity, potency and efficacy of tramadol and its metabolites at the cloned human µ-opioid receptor

  title={Affinity, potency and efficacy of tramadol and its metabolites at the cloned human µ-opioid receptor},
  author={Clemens Gillen and Michael Haurand and D. Kobelt and Stephan Wnendt},
  journal={Naunyn-Schmiedeberg's Archives of Pharmacology},
Abstract. The present study was conducted to characterise the centrally active analgesic drug tramadol hydrochloride [(1RS,2RS)-2-[(dimethyl-amino)-methyl]-1-(3-methoxyphenyl)-cyclohexanol hydrochloride] and its metabolites M1, M2, M3, M4 and M5 at the cloned human µ-opioid receptor. Membranes from stably transfected Chinese hamster ovary (CHO) cells were used to determine the four parameters of the ligand-receptor interaction: the affinity of (±)-tramadol and its metabolites was determined by… 
Antinociceptive profile of LP1, a non-peptide multitarget opioid ligand.
Clinical Pharmacology of Tramadol
Tramadol is an effective and well tolerated agent to reduce pain resulting from trauma, renal or biliary colic and labour, and also for the management of chronic pain of malignant or nonmalignant origin, particularly neuropathic pain.
µ-Opioid receptor activation by tramadol and O-desmethyltramadol (M1)
The effects of tramadol and its main active metabolite O-desmethyltramadol (M1), on the function of µ ORs using Xenopus oocytes expressing cloned human µORs are examined.
Design, synthesis and biological evaluation of N-phenylalkyl-substituted tramadol derivatives as novel μ opioid receptor ligands
Unlike morphine-derived structures in which bulky N-substitution is associated with improved opioid-like activities, there seems to be a different story for tramadol, suggesting the potential difference of SAR between these compounds.
Uptake/Efflux Transport of Tramadol Enantiomers and O-Desmethyl-Tramadol: Focus on P-Glycoprotein
Proton-based efflux pumps may be involved in limiting the gastrointestinal absorption of TMDEnantiomers as well as enhancing TMD enantiomers and M1 renal excretion and a possible involvement of uptake carriers in the transepithelial transport of T MD enantiomer and M 1 is suggested.
Discovery of Potent and Selective Agonists of δ Opioid Receptor by Revisiting the "Message-Address" Concept.
A series of novel compounds that act as highly potent and selective agonists of DOR among which (-)-6j showed the highest affinity, best agonistic activity, and DOR selectivity are designed.
Inhibition of L-type calcium current by tramadol and enantiomers in cardiac myocytes from rats.
The inhibition of ICa-L induced by tramadol and its enantiomers was unrelated to the activation of opioid receptors and could explain, at least in part, their negative cardiac inotropic effect.


Influence of tramadol on neurotransmitter systems of the rat brain.
The results indicate that tramadol enhances DA turnover via an opioid mechanism and closely resembles that of NA and 5-HT uptake inhibitors.
[Duality of the analgesic effect of tramadol in humans].
It is concluded that tramadol analgesia is only partially mediated by a mu opioid agonist effect, which results from an action on opioid receptors other than the mu subtype and/or from nonopioid effects (monoaminergic system).
Complementary and synergistic antinociceptive interaction between the enantiomers of tramadol.
A rational explanation for the coexistence of dual components to tramadol-induced antinociception appears to be related to the different, but complementary and interactive, pharmacologies of its enantiomers and might form the basis for understanding its clinical profile.
Efficacy and tolerance of narcotic analgesics at the mu opioid receptor in differentiated human neuroblastoma cells.
  • V. Yu, W. Sadee
  • Biology, Medicine
    The Journal of pharmacology and experimental therapeutics
  • 1988
The differentiated SH-SY5Y cells provide a suitable system for studying the molecular mechanisms of the narcotic analgesics, which suggests that this cell model could provide a rapid screening assay for Narcotic analgesic efficacy.
Characterization of opioid agonist efficacy in a C6 glioma cell line expressing the mu opioid receptor.
The results presented show that the stable expression of the rat mu opioid receptor in C6 cells provides an effective tool to examine opioid receptor signal transduction mechanisms and evaluate the activity of novel opioids at the mu receptor.
Characterization of the unusual antinociceptive profile of tramadol in mice
The lack of complete cross‐tolerance between tramadol and morphine supports the suggestion of a non‐opioid mechanism for this compound, whereas the complete antagonism by naloxone apparently reflects the opioid component of its mechanism in this test.
Characterization of the cloned human mu opioid receptor.
The human homolog of the mu opioid receptor has high affinities for several alkaloids of high abuse potential as well as a variety of peptide and nonpeptide drugs characterized previously as mu-selective, but not delta- or kappa- selective.
Assessment of relative intrinsic activity of mu-opioid analgesics in vivo by using beta-funaltrexamine.
Fentanyl and methadone have higher intrinsic efficacies than do morphine and levorphanol, and a strategy used widely in vitro was applied successfully in vivo to assess relative intrinsic activities of a series of mu-opioid agonists.