Abstract
A series consisting of spiroindanyl (5-7), benzospiroindanyl (8-10), and spiroperinaphthyl (11) derivatives of naltrexone and oxymorphone were synthesized in order to investigate the role of an orthogonal-oriented "address" for delta opioid receptors. All of the ligands exhibited a preference for delta receptors in vitro. The 7-benzospiroindanyl derivative 8 (BSINTX) was the most selective delta opioid receptor antagonist in vitro. In mice BSINTX antagonized the delta 1-selective agonist, [D-Pen2,D-Pen5]enkephalin without significantly affecting the antinociceptive potency of delta 2, mu, and kappa agonists. The results of this study are consistent with an orthogonally-oriented address favoring delta 1 activity.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Analgesia
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Analgesics
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Animals
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Brain / metabolism
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Cell Membrane / metabolism
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Enkephalin, D-Penicillamine (2,5)-
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Enkephalins / antagonists & inhibitors
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Enkephalins / metabolism
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Guinea Pigs
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Ileum
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Ligands
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Male
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Mice
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Mice, Inbred ICR
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Molecular Structure
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Muscle, Smooth / drug effects
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Muscle, Smooth / physiology
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Naltrexone / analogs & derivatives*
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Naltrexone / chemical synthesis
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Naltrexone / metabolism
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Naltrexone / pharmacology
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Oxymorphone / analogs & derivatives*
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Receptors, Opioid, delta / agonists
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Receptors, Opioid, delta / antagonists & inhibitors
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Receptors, Opioid, delta / metabolism*
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Spiro Compounds / chemical synthesis*
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Spiro Compounds / metabolism
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Spiro Compounds / pharmacology*
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Vas Deferens
Substances
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7-(5',6'-benzo-2'-spiroindanyl)naltrexone
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Analgesics
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Enkephalins
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Ligands
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Receptors, Opioid, delta
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Spiro Compounds
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Naltrexone
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Enkephalin, D-Penicillamine (2,5)-
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Oxymorphone