Abstract
Ethylketocyclazocine (1) has greater kappa/mu selectivity than cyclazocine in brain binding assays. 10-Ketonaltrexone (11) and 10-ketooxymorphone (10) were prepared from naltrexone 3-methyl ether and oxycodone, respectively. Bioassays in the myenteric plexus longitudinal muscle preparation of the guinea pig ileum and in the mouse vas deferens, in addition to brain binding assays, demonstrated that 10 and 11 were far less potent than naltrexone (2) and oxymorphone (3) at mu sites and also had little affinity for kappa and delta sites. It is concluded that introduction of the 10-keto group in naltrexone and oxymorphone diminished opioid effects at all binding sites.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Biological Assay
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Brain / metabolism
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Chemical Phenomena
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Chemistry
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Guinea Pigs
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Hydromorphone / analogs & derivatives*
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Ileum / drug effects
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Male
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Mice
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Naloxone / analogs & derivatives*
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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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Oxymorphone / chemical synthesis
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Oxymorphone / metabolism
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Oxymorphone / pharmacology*
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Receptors, Opioid / drug effects
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Receptors, Opioid / physiology
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Structure-Activity Relationship
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Vas Deferens / drug effects
Substances
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Receptors, Opioid
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Naloxone
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Naltrexone
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10-ketonaltrexone
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10-ketooxymorphone
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Oxymorphone
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Hydromorphone