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• W2076436113 abstract "Two novel oxime derivatives of naltrexone, 6-[2-phenylethyl]-oximino naltrexone (NPC 831) and 6-[3-phenylpropyl]-oximino naltrexone (NPC 836) were potent agonists at opioid receptors. Both compounds inhibited binding to all three opioid receptor subtypes with nanomolar affinities. In vivo, NPC 831 and NPC 836 were equipotent to morphine and more potent than the kappa-selective agonist U-50,488H to produce analgesia. ED50 values of 4.02 mg/kg for NPC 831 and 2.24 mg/kg for NPC 836 were generated for inhibition of the tail-flick response in the rat, and ED50 values of 0.05 mg/kg for NPC 831 and 0.02 mg/kg for NPC 836 were calculated for inhibition of the writhing response in the mouse. Bombesin-induced scratching was used to evaluate NPC 831 and NPC 836 for kappa-agonist properties, and the A50, defined as the percent antagonism of the bombesin-induced response, was 1.86 mg/kg for NPC 831 and 0.08 mg/kg for NPC 836, compared to an A50 of 1.54 mg/kg for U-50,488H. These data suggest that NPC 831 and NPC 836 possess potent mu- and kappa-agonist properties in vivo, with NPC 836 being approximately twice as potent as NPC 831 to produce analgesia and 20 times as potent as NPC 831 to inhibit the scratching response produced by bombesin." @default.
• W2076436113 created "2016-06-24" @default.
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• W2076436113 date "1993-01-01" @default.
• W2076436113 modified "2023-09-26" @default.
• W2076436113 title "Opioid agonist properties of two oxime derivatives of naltrexone, NPC 831 and NPC 836" @default.
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• W2076436113 doi "https://doi.org/10.1016/0091-3057(93)90279-3" @default.
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