Abstract
Receptor binding assays using [3H]DAGO ([D-Ala2,MePhe4-Gly5-ol]enkephalin) (mu), [3H]DPDPE ([D-Pen2,D-Pen5]enkephalin) (delta) and [3H]U-69593 (kappa) were done in guinea pig whole brain membranes. Agonist activity was determined in norbinaltorphimine or beta-funaltrexamine (beta-FNA) treated guinea pig ileum (mu and kappa, respectively) and beta-FNA-treated mouse vas deferens (delta). The compounds with highest affinity were the most potent at the mu-receptor. The selectivity observed in the binding affinities was also found in in vitro activity. No correlation was found between mu-affinity and selectivity; the highest affinity analog, lofentanil, was found to be among the least selective, while another high affinity analog, R30490, was the most mu-selective. The results show that not all fentanyls are highly mu-selective, and could produce actions through delta- and kappa-opiate receptors.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Analgesics, Opioid / metabolism
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Animals
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Benzeneacetamides*
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Brain / metabolism
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
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Enkephalin, D-Penicillamine (2,5)-
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Enkephalins / metabolism*
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Fentanyl / analogs & derivatives*
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Fentanyl / metabolism
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Guinea Pigs
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Ileum / drug effects
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Ileum / metabolism
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Male
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Mice
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Naltrexone / analogs & derivatives
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Naltrexone / pharmacology
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Pyrrolidines / metabolism*
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Receptors, Opioid / metabolism*
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Receptors, Opioid, delta
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Receptors, Opioid, kappa
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Receptors, Opioid, mu
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Vas Deferens / drug effects
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Vas Deferens / metabolism
Substances
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Analgesics, Opioid
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Benzeneacetamides
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Enkephalins
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Pyrrolidines
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Receptors, Opioid
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Receptors, Opioid, delta
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Receptors, Opioid, kappa
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Receptors, Opioid, mu
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
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norbinaltorphimine
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Naltrexone
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4-methoxymethylfentanyl
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beta-funaltrexamine
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lofentanil
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Enkephalin, D-Penicillamine (2,5)-
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U 69593
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Fentanyl