Abstract
The Aba-Gly scaffold, incorporated into Dmt-Tic ligands (H-Dmt-Tic-Gly-NH-CH2-Ph, H-Dmt-Tic-Gly-NH-Ph, H-Dmt-Tic-NH-CH2-Bid), exhibited mixed micro/delta or delta opioid receptor activities with micro agonism. Substitution of Tic by Aba-Gly coupled to -NH-CH2-Ph (1), -NH-Ph (2), or -Bid (Bid=1H-benzimidazole-2-yl) (3) shifted affinity (Ki(micro)=0.46, 1.48, and 19.9 nM, respectively), selectivity, and bioactivity to micro-opioid receptors. These compounds represent templates for a new class of lead opioid agonists that are easily synthesized and suitable for therapeutic pain relief.
Publication types
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Analgesics, Opioid / chemical synthesis*
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Analgesics, Opioid / chemistry
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Analgesics, Opioid / pharmacology
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Animals
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Benzazepines / chemical synthesis*
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Benzazepines / pharmacology
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Glycine / analogs & derivatives*
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Glycine / chemical synthesis*
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Glycine / pharmacology
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Guinea Pigs
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In Vitro Techniques
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Ligands
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Molecular Mimicry
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Muscle Contraction / drug effects
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Muscle, Smooth / drug effects
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Muscle, Smooth / innervation
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Muscle, Smooth / physiology
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Myenteric Plexus / physiology
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Peptides / chemistry*
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Rats
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Rats, Sprague-Dawley
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Receptors, Opioid, delta / metabolism
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Receptors, Opioid, mu / agonists*
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Structure-Activity Relationship
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Synaptosomes / drug effects
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Synaptosomes / metabolism
Substances
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Analgesics, Opioid
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Benzazepines
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Ligands
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Peptides
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Receptors, Opioid, delta
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Receptors, Opioid, mu
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Glycine