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PubMed · 8164264

Structural features important for sigma 1 receptor binding.

R A Glennon·S Y Ablordeppey·A M Ismaiel·M B el-Ashmawy·J B Fischer·K B Howie
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Abstract

Two problems that have hampered sigma receptor research are (i) a lack of high-affinity agents and (ii) the recent identification of multiple populations of sigma receptors (i.e., sigma 1 and sigma 2 sites). Recently, several high-affinity sigma ligands have been identified, and the term superpotent sigma ligands has been coined to describe agents with Ki values of < 1 nM. We have previously shown that appropriately N-substituted phenylalkylamines bind at sigma receptors with high affinity. In the present investigation, we examine the structure-affinity relationships of these phenylalkylamine derivatives for sigma 1 binding and describe some of the first superpotent sigma 1 ligands. A binding model was developed to account for the structural features of the phenylalkylamines that appear to be important for the interaction of these agents with sigma 1 sites.

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AlkylationAminesAnimalsBinding SitesBrainCell MembraneCyclizationGuinea PigsMethylationMolecular StructureReceptors, sigmaStereoisomerismStructure-Activity RelationshipComparative StudyJournal Article

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R A Glennon, S Y Ablordeppey, A M Ismaiel, M B el-Ashmawy, J B Fischer, K B Howie. 1994-04-15. Structural features important for sigma 1 receptor binding.. https://doi.org/10.1021/jm00034a020

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