Anionic receptor sites opiate

Interaction of Model Opiate Anionic Receptor Sites with Characteristic JV-Substituents of Rigid Opiates PCILO and Empirical Potential Energy Calculations... 

In this study both the PCILO and empirical energy methods were used to characterize intermolecular interactions of typical N-substituents of rigid opiates with model anionic receptor sites. Ammonium methylphosphate (AMP) and ammonium methylsulfate (AMS) were used as model anionic receptor sites. Interaction energies of eight compounds which, as N-substituents. modulate different antagonist/agonist potencies... 

With the exception of the cyclopropylmetbane, the main discrepancy is the relatively large energy calculated for the 2,3 - dimethylfuran. The stabilization energies of the AMS complexes calculated by the empirical method correlate more with the measured affinities and antagonist potencies than those for the AMP complexes. Additionally, more stable complexes with AMS are found by the empirical method than by the PCILO method. Taken together, the results of both methods indicate that either the phosphate or sulfate anion is a reasonable model for the anionic opiate receptor site. 

One possible form of Ca +-opiate interaction is drug-induced inhibition of Ca + binding at synaptic membrane sites. However, as we have discussed previously the evidence for such an effect in vitro is equivocal. Mule (74) has proposed that opiates displace Ca + from anionic binding sites on phospholipid molecules in neuronal membranes. The displacement of Ca + from these phospholipid opiate receptors would thus result in changes in membrane permeability to other ions, producing alterations in neuronal excitability. 

Befort K, Tabbara L, Bausch S et al. The conserved aspartate residue in the third putative transmembrane domain of the <5-opioid receptor is not the anionic counterion for cationic opiate binding but is a constituent of the receptor binding site. Mol Pharmacol 1996 49 216-223. 

In 1954, Beckett and Casy [214] proposed an anionic site on the opiate receptor to account for bonding of opiate agonists and antagonists which were recognized as having a cationic component at biological pH values as shown in Scheme 6.1. Subsequently, a great deal of research was done to increase... 

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