Abstract
An SAR study on the Dmt-substituted enkephalin-like tetrapeptide with a N-phenyl-N-piperidin-4-ylpropionamide moiety at the C-terminal was performed and has resulted in highly potent ligands at μ and δ opioid receptors. In general, ligands with the substitution of D-Nle(2) and halogenation of the aromatic ring of Phe(4) showed highly increased opioid activities. Ligand 6 with good biological activities in vitro demonstrated potent in vivo antihyperalgesic and antiallodynic effects in the tail-flick assay.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amides / chemical synthesis
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Amides / chemistry
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Amides / pharmacology
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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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Binding, Competitive
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CHO Cells
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Cell Membrane Permeability
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Cricetinae
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Cricetulus
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Humans
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Hyperalgesia / drug therapy
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Ileum / drug effects
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Ileum / physiology
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In Vitro Techniques
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Ligands
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Male
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Mice
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Muscle, Smooth / drug effects
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Muscle, Smooth / physiology
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Neuralgia / drug therapy
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Oligopeptides / chemical synthesis*
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Oligopeptides / chemistry
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Oligopeptides / pharmacology
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Piperidines / chemical synthesis*
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Piperidines / chemistry
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Piperidines / pharmacology
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Propionates / chemical synthesis
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Propionates / chemistry
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Propionates / pharmacology
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Radioligand Assay
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Rats
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Rats, Sprague-Dawley
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Receptors, Opioid, delta / agonists*
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Receptors, Opioid, mu / agonists*
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Structure-Activity Relationship
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Vas Deferens / drug effects
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Vas Deferens / physiology
Substances
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Amides
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Analgesics, Opioid
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Ligands
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Oligopeptides
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Piperidines
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Propionates
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Receptors, Opioid, delta
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Receptors, Opioid, mu