Abstract
Continuing our studies investigating opioids with reduced P-glycoprotein (P-gp) substrate activity, a series of known 3- and 6-hydroxy, -methoxy, and -desoxymorphine analogs was synthesized and analyzed for P-gp substrate activity and opioid binding affinity. 6-Desoxymorphine ( 7) showed high affinity for opioid receptors and did not induce P-gp-mediated ATP hydrolysis. Additionally, 7 demonstrated morphine-like antinociceptive potency in mice, indicating this compound as an ideal lead to further evaluate the role of P-gp in opioid analgesic tolerance development.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B / drug effects*
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Analgesics, Non-Narcotic / administration & dosage
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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 Sites
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CHO Cells
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Cell Line, Tumor
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Cricetinae
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Cricetulus
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Mice
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Molecular Conformation
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Morphine Derivatives / chemical synthesis
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Morphine Derivatives / chemistry
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Morphine Derivatives / pharmacology*
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Pain Measurement / drug effects
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Rats
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Receptors, Opioid / drug effects
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Stereoisomerism
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Structure-Activity Relationship
Substances
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6-desoxymorphine
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ATP Binding Cassette Transporter, Subfamily B
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Analgesics, Non-Narcotic
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Analgesics, Opioid
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Morphine Derivatives
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Receptors, Opioid