The Experts below are selected from a list of 24 Experts worldwide ranked by ideXlab platform
Anthony L Riley - One of the best experts on this subject based on the ideXlab platform.
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Nalorphine s ability to substitute for morphine in a drug discrimination procedure is a function of training dose
Pharmacology Biochemistry and Behavior, 1999Co-Authors: Sheri D Grabus, Scott T Smurthwaite, Anthony L RileyAbstract:Rats trained to discriminate the mu agonists fentanyl or morphine from their respective vehicles generalize to the partial mu agonist Nalorphine incompletely and inconsistently. Any number of factors may influence the generalization patterns obtained, one of which being the specific dose of the full opioid agonist used during training, a factor reported to influence generalization with other partial opioid agonists. To assess if training dose influences stimulus generalization to Nalorphine and to support its role in the aforementioned variability across studies, in the present experiments rats were trained to discriminate either a low (5.6 mg/kg) or a high (10 mg/kg) dose of morphine from distilled water within the taste aversion baseline of drug discrimination learning. Subjects were then given a range of doses of morphine, Nalorphine, methadone, or naloxone to assess the degree of substitution (if any) of these compounds for the training dose of morphine. For all subjects, morphine fully substituted for itself, and the opioid antagonist naloxone failed to substitute for the morphine cue. Rats generalized the morphine cue to Nalorphine in subjects trained at the lower dose but not in subjects trained at the higher dose. Rats generalized the morphine cue to methadone in the latter group (the high dose group), indicating that the failure to generalize to Nalorphine in this group was not a general inability of an opioid agonist to substitute for morphine. Naloxone blocked morphine stimulus control in all subjects and Nalorphine control in the low-dose group for which Nalorphine substituted for morphine, suggesting that morphine control (and the Nalorphine substitution) was based on opioid activity. These results indicate that the substitution patterns of Nalorphine in morphine-trained subjects are a function in part of the dose of morphine used in training and support the position that Nalorphine is a partial opioid agonist with intermediate efficacy.
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Nalorphine as a stimulus in drug discrimination learning assessment of the role of μ and κ receptor subtypes
Pharmacology Biochemistry and Behavior, 1994Co-Authors: Scott T Smurthwaite, Anthony L RileyAbstract:Using the conditioned taste aversion baseline of drug discrimination learning, animals were trained to discriminate Nalorphine from distilled water. In subsequent generalization tests, the mu-opiate agonist morphine substituted for the Nalorphine stimulus in a dose-dependent manner, while the kappa-opiate agonist U50,488H and the mu-opiate antagonists naloxone and naltrexone failed to do so. That the mu-agonist morphine substituted for the Nalorphine stimulus while a kappa-agonist and mu-antagonists failed to substitute indicate that the discriminative control that was established with Nalorphine in the present study was mu-agonist receptor-mediated. The basis for this selective control by the mu-receptor subtype may be related to the relative salience of receptor activity in opiate-naive animals. The present results suggest that discriminative control by compounds with activity at multiple receptor sites is not uniformly mediated by specific activity at all of those sites. The specific site mediating discriminative control appears to be a function of the specific training drug.
Gavril W Pasternak - One of the best experts on this subject based on the ideXlab platform.
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pharmacological characterization of Nalorphine a kappa 3 analgesic
Journal of Pharmacology and Experimental Therapeutics, 1991Co-Authors: Dennis Paul, Chaim G Pick, L Tive, Gavril W PasternakAbstract:Nalorphine is an unusual opiate. Whereas low doses of Nalorphine antagonize morphine analgesia, higher Nalorphine doses are analgesic, with ED50 values (95% CL) of 13.4 (11.5, 15.8) mg/kg in the writhing and 39.5 (26.6, 60.1) mg/kg in the tail-flick assay. Although Nalorphine analgesia is sensitive to naloxone, implying an opioid mechanism, neither beta-funaltrexamine, naltrindole nor nor-binaltorphomine antagonized Nalorphine analgesia in the tail-flick assay at doses which reversed equianalgesic doses of their respective selective agonists. Nalorphine and the kappa 3 opiate naloxone benzoylhydrazone demonstrated analgesic cross-tolerance regardless of whether the mice were treated chronically with either Nalorphine or naloxone benzoylhydrazone. Animals tolerant to Nalorphine were not tolerant to either morphine or U50,488H (trans-3,4-dichloro-N-methyl-N-[2-(pyrrolindinyl)-cyclohexyl]- benzeneacetamide). Furthermore, Nalorphine retained its analgesic potency in animals tolerant to U50,488H. Nalorphine exerts its analgesia predominantly through supraspinal mechanisms. Against systemically administered Nalorphine, the opiate antagonist WIN44,441 ([2,6,11S-(-)-1-cyclopentyl-5-(1,2,3,4,5,6-hexahydro-8-hydroxy-3,6, 11-trimethyl-2,6-methano-e-benazocine-11-yl)-3-pentanone methylsulfonate) reversed Nalorphine analgesia 1500-fold more potently when administered i.c.v. (ID50, 0.1 ng) than when given intrathecally (ID50,159 ng). Together these results indicate that Nalorphine analgesia in the tail-flick assay does not involve mu, delta or the U50,488H-sensitive kappa 1 receptor and strongly suggest a role for supraspinal kappa 3 receptors.
Scott T Smurthwaite - One of the best experts on this subject based on the ideXlab platform.
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Nalorphine s ability to substitute for morphine in a drug discrimination procedure is a function of training dose
Pharmacology Biochemistry and Behavior, 1999Co-Authors: Sheri D Grabus, Scott T Smurthwaite, Anthony L RileyAbstract:Rats trained to discriminate the mu agonists fentanyl or morphine from their respective vehicles generalize to the partial mu agonist Nalorphine incompletely and inconsistently. Any number of factors may influence the generalization patterns obtained, one of which being the specific dose of the full opioid agonist used during training, a factor reported to influence generalization with other partial opioid agonists. To assess if training dose influences stimulus generalization to Nalorphine and to support its role in the aforementioned variability across studies, in the present experiments rats were trained to discriminate either a low (5.6 mg/kg) or a high (10 mg/kg) dose of morphine from distilled water within the taste aversion baseline of drug discrimination learning. Subjects were then given a range of doses of morphine, Nalorphine, methadone, or naloxone to assess the degree of substitution (if any) of these compounds for the training dose of morphine. For all subjects, morphine fully substituted for itself, and the opioid antagonist naloxone failed to substitute for the morphine cue. Rats generalized the morphine cue to Nalorphine in subjects trained at the lower dose but not in subjects trained at the higher dose. Rats generalized the morphine cue to methadone in the latter group (the high dose group), indicating that the failure to generalize to Nalorphine in this group was not a general inability of an opioid agonist to substitute for morphine. Naloxone blocked morphine stimulus control in all subjects and Nalorphine control in the low-dose group for which Nalorphine substituted for morphine, suggesting that morphine control (and the Nalorphine substitution) was based on opioid activity. These results indicate that the substitution patterns of Nalorphine in morphine-trained subjects are a function in part of the dose of morphine used in training and support the position that Nalorphine is a partial opioid agonist with intermediate efficacy.
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Nalorphine as a stimulus in drug discrimination learning assessment of the role of μ and κ receptor subtypes
Pharmacology Biochemistry and Behavior, 1994Co-Authors: Scott T Smurthwaite, Anthony L RileyAbstract:Using the conditioned taste aversion baseline of drug discrimination learning, animals were trained to discriminate Nalorphine from distilled water. In subsequent generalization tests, the mu-opiate agonist morphine substituted for the Nalorphine stimulus in a dose-dependent manner, while the kappa-opiate agonist U50,488H and the mu-opiate antagonists naloxone and naltrexone failed to do so. That the mu-agonist morphine substituted for the Nalorphine stimulus while a kappa-agonist and mu-antagonists failed to substitute indicate that the discriminative control that was established with Nalorphine in the present study was mu-agonist receptor-mediated. The basis for this selective control by the mu-receptor subtype may be related to the relative salience of receptor activity in opiate-naive animals. The present results suggest that discriminative control by compounds with activity at multiple receptor sites is not uniformly mediated by specific activity at all of those sites. The specific site mediating discriminative control appears to be a function of the specific training drug.
Dennis Paul - One of the best experts on this subject based on the ideXlab platform.
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pharmacological characterization of Nalorphine a kappa 3 analgesic
Journal of Pharmacology and Experimental Therapeutics, 1991Co-Authors: Dennis Paul, Chaim G Pick, L Tive, Gavril W PasternakAbstract:Nalorphine is an unusual opiate. Whereas low doses of Nalorphine antagonize morphine analgesia, higher Nalorphine doses are analgesic, with ED50 values (95% CL) of 13.4 (11.5, 15.8) mg/kg in the writhing and 39.5 (26.6, 60.1) mg/kg in the tail-flick assay. Although Nalorphine analgesia is sensitive to naloxone, implying an opioid mechanism, neither beta-funaltrexamine, naltrindole nor nor-binaltorphomine antagonized Nalorphine analgesia in the tail-flick assay at doses which reversed equianalgesic doses of their respective selective agonists. Nalorphine and the kappa 3 opiate naloxone benzoylhydrazone demonstrated analgesic cross-tolerance regardless of whether the mice were treated chronically with either Nalorphine or naloxone benzoylhydrazone. Animals tolerant to Nalorphine were not tolerant to either morphine or U50,488H (trans-3,4-dichloro-N-methyl-N-[2-(pyrrolindinyl)-cyclohexyl]- benzeneacetamide). Furthermore, Nalorphine retained its analgesic potency in animals tolerant to U50,488H. Nalorphine exerts its analgesia predominantly through supraspinal mechanisms. Against systemically administered Nalorphine, the opiate antagonist WIN44,441 ([2,6,11S-(-)-1-cyclopentyl-5-(1,2,3,4,5,6-hexahydro-8-hydroxy-3,6, 11-trimethyl-2,6-methano-e-benazocine-11-yl)-3-pentanone methylsulfonate) reversed Nalorphine analgesia 1500-fold more potently when administered i.c.v. (ID50, 0.1 ng) than when given intrathecally (ID50,159 ng). Together these results indicate that Nalorphine analgesia in the tail-flick assay does not involve mu, delta or the U50,488H-sensitive kappa 1 receptor and strongly suggest a role for supraspinal kappa 3 receptors.
Harold V Street - One of the best experts on this subject based on the ideXlab platform.
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a note on the paper chromatographic separation of codeine morphine and Nalorphine
Journal of Pharmacy and Pharmacology, 2011Co-Authors: Harold V StreetAbstract:Codeine has been separated from a mixture of codeine, morphine and Nalorphine on Whatman ET20 ion-exchange paper, in 5 min. A mixture of morphine and Nalorphine has been separated in 90 min. by horizontal circular reversed phase paper chromatography. Using ascending chromatography at 86° on tributyrin-treated paper, an unequivocal resolution of a mixture of morphine, Nalorphine and codeine has been achieved within 20 min.
