Opioid ligands interaction

Opioid-Chemokine Interactions 16.2.1 Chemokine Ligands and Receptors... 

Bolan EA, Tallarida RJ, Pasternak GW Synergy between mu opioid ligands Evidence for functional interactions among mu opioid receptor subtypes. J Pharmacol Exp Ther 2002 303 557. [PMID 12388636]... 

Portoghese, P.S., Alreja, B.D., Larson, D.L. Allylprodine analogues as receptor probes. Evidence that phenolic and nonphenolic ligands interact with different subsites on identical opioid receptors, J. Med. Chem. 1981, 24, 782-787. 

A series of cyclic conformationally constrained peptides related to somatostatin were designed, synthesized and tested for opioid receptor interaction by Hruby and his collaborators. Compounds (17)-(22) were found to be pure opioid antagonists (GPI) with high affinity (IC50 = 1.2 to 4.3 nM) and exceptional selectivity for p over S opioid receptors (Table 3.1) and with minimal or no somatostatin-like activity (ligand binding assays)[63-65]. 

There is ample evidence of the importance of the relative placement and orientation of aromatic features to the rest of the molecule (notably the. basic area) in active derivatives, and binding interactions involving the basic and aromatic features of the ligand must be of primary importance in opioid receptor-ligand interactions. One example of the influence of phenyl orientation relative to the rest of the molecule is Portoghese s explanation of structure-activity variations among antipodal prodines and related compounds, as discussed in Chapter 7. 

The role of oxygen functions in opioid ligands is complex, involving distribution, metabolism (especially conjugation) and binding interactions with the receptor, and assessment of the significance of a particular group requires information on each of these aspects. 

Fig 1311 Hypothetical model for ligand interactions with the opioid receptor (Only k-8 hetero oligomers shown, but scheme also applies to the complex) The interactions between the... 

These studies demonstrate the complexities of ligand binding to opioid receptors and indicate that more research is required to more fully understand, at the molecular level, the interactions of different opioid ligands with their receptors. 

Because of the side effects associated with analgesics that interact with fi opioid receptors, there has been considerable interest in developing opioid ligands that interact with other opioid receptors. In addition to analgesic activity, there are a number of other potential therapeutic applications of ligands, both agonists and antagonists, for non-p, opioid receptors. 

Affinity labels, ligands that interact with receptors in a nonequilibrium manner, are useful pharmacological tools to study opioid receptors and receptor-ligand interactions. 

All of the current opioid drugs used for the treatment of pain are primarily ligands for the p-opioid receptor. Numerous studies since the discovery of enkephalin 27 years ago (210) have suggested that an opioid ligand that primarily interacted with the 6-opioid receptor would have far fewer of the toxicities generally associated with the p,-opioid ligand (respiratory depression, constipation, addiction, etc.). 

Ananthan S. Opioid ligands with mixed mu/delta opioid receptor interactions an emerging approach to novel analgesics. AAPS J 2006 8 El 18-25. 

Tab. 3.2 Examples of thermodynamic studies of ligand interaction with opioid receptors (from...

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