6-Monoacetylmorphine

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Simona Pichini - One of the best experts on this subject based on the ideXlab platform.

  • Development and validation of a gas chromatography-mass spectrometry assay for opiates and cocaine in human teeth.
    Journal of pharmaceutical and biomedical analysis, 2005
    Co-Authors: Manuela Pellegrini, Roberta Pacifici, Emilia Marchei, Oscar Garcia-algar, Adriana Casá, Ruth Mayné, Vanessa Barbero, Simona Pichini
    Abstract:

    Abstract A procedure based on gas chromatography–mass spectrometry (GC–MS) is described for determination of opiates (6-Monoacetylmorphine, morphine and codeine) and cocaine and metabolites (cocaine, benzoylecgonine and cocaethylene) in human teeth. After addition of nalorphine as internal standard, pulverized samples were incubated in HCl at 37 °C for 18 h. Then, after pH adjustment to 6, and the analytes were extracted with two volumes of 3 ml of chloroform/isopropanol (9:1). Chromatography was performed on a fused silica capillary column and analytes were determined in the selected-ion-monitoring (SIM) mode. The assay was validated in the range 7.5 (6.0 in case of codeine) to 500 ng/g with mean absolute recoveries ranged between 74.1 and 92.1% for the different analytes and precision and accuracy always better than 15%. The method was applied to the analysis of teeth from drug-addicts to assess past chronic consumption and verify self-reported declarations. In case of opiates, concentration range was 36.5–570.0 ng/g for 6-Monoacetylmorphine, 8.7–154.8 ng/g for morphine and 7.9–127.9 ng/g for codeine. Cocaine concentration ranged between 5.6 and 57.2 ng/g with its principal metabolite benzoylecgonine varying from 12.6 to 81.7 ng/g and cocaethylene present in only one sample at 10 ng/g value. Teeth can be a promising non-invasive biological matrix in biomedical analysis for both clinical and forensic purposes.

  • Development and validation of a liquid chromatography-mass spectrometry assay for the determination of opiates and cocaine in meconium.
    Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2003
    Co-Authors: Simona Pichini, Roberta Pacifici, Manuela Pellegrini, Emilia Marchei, E. Perez-alarcòn, C. Puig, Oriol Vall, Oscar Garcia-algar
    Abstract:

    A procedure based on liquid chromatography-mass spectrometry (LC-MS) is described for determination of 6-Monoacetylmorphine, morphine, morphine-3-glucuronide, morphine-6-glucuronide, codeine, cocaine, benzoylecgonine and cocaethylene in meconium using nalorfine as the internal standard. The analytes are initially extracted from the matrix by methanol (6-Monoacetylmorphine, morphine, codeine, cocaine, benzoylecgonine and cocaethylene) or 0.01 M ammonium hydrogen carbonate buffer (morphine-3-glucuronide, morphine-6-glucuronide). Subsequently a solid-phase extraction with Bondelut Certify columns (6-Monoacetylmorphine, morphine, codeine, cocaine, benzoylecgonine and cocaethylene) or ethyl solid-phase extraction columns (morphine-3-glucuronide, morphine-6-glucuronide) was applied. Chromatography was performed on a C(8) reversed-phase column using a gradient of acetic acid 1%-acetonitrile as a mobile phase. Analytes were determined in LC-MS single ion monitoring mode with atmospheric pressure ionisation-electrospray (ESI) interface. The method was validated in the range 0.005-1.00 microg/g using 1 g of meconium per assay and applied to analysis of meconium in newborns to assess fetal exposure to opiates and cocaine.

  • Analysis of opiates in human hair by high-performance liquid chromatography
    Journal of Liquid Chromatography & Related Technologies, 1999
    Co-Authors: Simona Pichini, Roberta Pacifici, Manuela Pellegrini, Ilaria Altieri, Piergiorgio Zuccaro
    Abstract:

    A high-performance liquid chromatographic method with ultraviolet radiation absorbance detection has been developed for the determination of the principal opiates (heroin, 6-Monoacetylmorphine, morphine, codeine) in human hair. An amount of 100 mg hair was incubated with 2 mL HCl 0.1 M at 56°C overnight and it was then extracted by solid-phase extraction using reversed-phase/ion exchange cartridges. Chromatography has been performed using a C18 reversed-phase column with a mobile phase consisting of water-acetonitrile (70:30 v/v) containing 0.01 M NaH2PO4 and 0.002 M sodium laurylsulphate at a final pH of 2.1. The linearity of the method was obtained in the concentration range of 0.5-50 ng/mg hair for 6-Monoacetylmorphine, morphine and codeine, and of 5–200 ng/mg hair for heroin. The accuracy of the methodology was assessed using reference material from National Institute of Standards and Technology consisting of human hair segments and powdered human hair soaked with opiates. Cocaine and benzoylecgonine ...

  • Simultaneous Determination of Heroin, 6-Monoacetylmorphine, Morphine, and its Glucuronides by Liquid Chromatography-Atmospheric Pressure Ionspray-Mass Spectrometry
    Journal of analytical toxicology, 1997
    Co-Authors: Piergiorgio Zuccaro, Simona Pichini, Roberta Pacifici, Manuela Pellegrini, R. Ricciarello, Ilaria Altieri, G. D'ascenzo
    Abstract:

    A new analytical technique has been developed for the simultaneous determination of heroin, 6-Monoacetylmorphine, morphine, morphine-6- and 3-glucuronides, and codeine in serum using liquid chromatography coupled with ionspray mass spectrometry. The analytes and the internal standard, nalorphine, were subjected to solid-phase extraction (SPE) using ethyl SPE columns before chromatography. The chromatographic separation of the analytes was achieved using a normal phase column and a water-methanol-acetonitrile-formic acid mobile phase at a flow rate of 230 microL/min. The mass spectrometer was operated in selected-ion monitoring mode. Under these conditions, the limit of quantitation was 0.5 ng/ml for heroin, 4 ng/ml for 6-Monoacetylmorphine, 4 ng/ml for morphine, 1 ng/ml for morphine-3-glucuronide, 4 ng/ml for morphine-6-glucuronide, and 4 ng/mL for codeine. Serum levels of heroin metabolites were determined in C57BL/6 inbred mice after a dose of 20 mg/kg heroin administered subcutaneously. 6-Monoacetylmorphine showed a peak concentration of 0.93 micrograms/mL serum at 3 min, whereas morphine and morphine-3-glucuronide achieved their peak concentrations of 9.6 and 2.9 micrograms/mL serum at 10 and 20 min, respectively. Finally, the absence of morphine-6-glucuronide and codeine excluded the possibility of their formation from morphine in this animal model.

Ulrike Kohls - One of the best experts on this subject based on the ideXlab platform.

  • Body Fluids Using One Isolation Procedure and Liquid Chromatography-Atmospheric-Pressure Chemical-Ionization Mass Spectrometry*
    2016
    Co-Authors: Maciej Bogusz J. T, Rolf-dieter Maier, Klaus-dieter Kriiger, Ulrike Kohls
    Abstract:

    Abstract I A method for determining opiate agonists (morphine, morphine-3-glucuronide, morphine-6-glucuronide, 6-Monoacetylmorphine, codeine, codeine-6-glucuronide, dihydrocodeine, dihydromorphine, buprenorphine, methadone, tramadol, and ibogaine), cocaine and its metabolites (benzoylecgonine and ecgonine methyl ester) and lysergic acid diethylamide in serum, blood, urine and other biological matrices is presented. Aliquots (0.5-1.5 mL) of biological fluids were spiked with appropriate deuterated internal standards and extracted using a common solid-phase extraction method (Ct8 cartridges). The extracts were subjected to liquid chromatographic-atmospheric-pressure chemical-ionization mass spectrometric examination using selected ion monitoring procedures. These procedures were developed after analysis of full-scan mass spectra of examined compounds. The extraction method appeared very universal; the recoveries were high for almost all drugs and the extracts were very clean. The procedure was applied for routine forensic casework

  • Determination of Common Drugs of Abuse in Body Fluids Using One Isolation Procedure and Liquid Chromatography-Atmospheric-Pressure Chemical-Ionization Mass Spectrometry
    Journal of Analytical Toxicology, 1998
    Co-Authors: Maciej J. Bogusz, Rolf-dieter Maier, Klaus-dieter Krüger, Ulrike Kohls
    Abstract:

    I A method for determining opiate agonists (morphine, morphine-3-glucuronide, morphine-6-glucuronide, 6-Monoacetylmorphine, codeine, codeine-6-glucuronide, dihydrocodeine, dihydromorphine, buprenorphine, methadone, tramadol, and ibogaine), cocaine and its metabolites (benzoylecgonine and ecgonine methyl ester) and lysergic acid diethylamide in serum, blood, urine and other biological matrices is presented. Aliquots (0.5-1.5 mL) of biological fluids were spiked with appropriate deuterated internal standards and extracted using a common solid-phase extraction method (Ct8 cartridges). The extracts were subjected to liquid chromatographic-atmospheric- pressure chemical-ionization mass spectrometric examination using selected ion monitoring procedures. These procedures were developed after analysis of full-scan mass spectra of examined compounds. The extraction method appeared very universal; the

Manuela Pellegrini - One of the best experts on this subject based on the ideXlab platform.

  • Development and validation of a gas chromatography-mass spectrometry assay for opiates and cocaine in human teeth.
    Journal of pharmaceutical and biomedical analysis, 2005
    Co-Authors: Manuela Pellegrini, Roberta Pacifici, Emilia Marchei, Oscar Garcia-algar, Adriana Casá, Ruth Mayné, Vanessa Barbero, Simona Pichini
    Abstract:

    Abstract A procedure based on gas chromatography–mass spectrometry (GC–MS) is described for determination of opiates (6-Monoacetylmorphine, morphine and codeine) and cocaine and metabolites (cocaine, benzoylecgonine and cocaethylene) in human teeth. After addition of nalorphine as internal standard, pulverized samples were incubated in HCl at 37 °C for 18 h. Then, after pH adjustment to 6, and the analytes were extracted with two volumes of 3 ml of chloroform/isopropanol (9:1). Chromatography was performed on a fused silica capillary column and analytes were determined in the selected-ion-monitoring (SIM) mode. The assay was validated in the range 7.5 (6.0 in case of codeine) to 500 ng/g with mean absolute recoveries ranged between 74.1 and 92.1% for the different analytes and precision and accuracy always better than 15%. The method was applied to the analysis of teeth from drug-addicts to assess past chronic consumption and verify self-reported declarations. In case of opiates, concentration range was 36.5–570.0 ng/g for 6-Monoacetylmorphine, 8.7–154.8 ng/g for morphine and 7.9–127.9 ng/g for codeine. Cocaine concentration ranged between 5.6 and 57.2 ng/g with its principal metabolite benzoylecgonine varying from 12.6 to 81.7 ng/g and cocaethylene present in only one sample at 10 ng/g value. Teeth can be a promising non-invasive biological matrix in biomedical analysis for both clinical and forensic purposes.

  • Development and validation of a liquid chromatography-mass spectrometry assay for the determination of opiates and cocaine in meconium.
    Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2003
    Co-Authors: Simona Pichini, Roberta Pacifici, Manuela Pellegrini, Emilia Marchei, E. Perez-alarcòn, C. Puig, Oriol Vall, Oscar Garcia-algar
    Abstract:

    A procedure based on liquid chromatography-mass spectrometry (LC-MS) is described for determination of 6-Monoacetylmorphine, morphine, morphine-3-glucuronide, morphine-6-glucuronide, codeine, cocaine, benzoylecgonine and cocaethylene in meconium using nalorfine as the internal standard. The analytes are initially extracted from the matrix by methanol (6-Monoacetylmorphine, morphine, codeine, cocaine, benzoylecgonine and cocaethylene) or 0.01 M ammonium hydrogen carbonate buffer (morphine-3-glucuronide, morphine-6-glucuronide). Subsequently a solid-phase extraction with Bondelut Certify columns (6-Monoacetylmorphine, morphine, codeine, cocaine, benzoylecgonine and cocaethylene) or ethyl solid-phase extraction columns (morphine-3-glucuronide, morphine-6-glucuronide) was applied. Chromatography was performed on a C(8) reversed-phase column using a gradient of acetic acid 1%-acetonitrile as a mobile phase. Analytes were determined in LC-MS single ion monitoring mode with atmospheric pressure ionisation-electrospray (ESI) interface. The method was validated in the range 0.005-1.00 microg/g using 1 g of meconium per assay and applied to analysis of meconium in newborns to assess fetal exposure to opiates and cocaine.

  • Analysis of opiates in human hair by high-performance liquid chromatography
    Journal of Liquid Chromatography & Related Technologies, 1999
    Co-Authors: Simona Pichini, Roberta Pacifici, Manuela Pellegrini, Ilaria Altieri, Piergiorgio Zuccaro
    Abstract:

    A high-performance liquid chromatographic method with ultraviolet radiation absorbance detection has been developed for the determination of the principal opiates (heroin, 6-Monoacetylmorphine, morphine, codeine) in human hair. An amount of 100 mg hair was incubated with 2 mL HCl 0.1 M at 56°C overnight and it was then extracted by solid-phase extraction using reversed-phase/ion exchange cartridges. Chromatography has been performed using a C18 reversed-phase column with a mobile phase consisting of water-acetonitrile (70:30 v/v) containing 0.01 M NaH2PO4 and 0.002 M sodium laurylsulphate at a final pH of 2.1. The linearity of the method was obtained in the concentration range of 0.5-50 ng/mg hair for 6-Monoacetylmorphine, morphine and codeine, and of 5–200 ng/mg hair for heroin. The accuracy of the methodology was assessed using reference material from National Institute of Standards and Technology consisting of human hair segments and powdered human hair soaked with opiates. Cocaine and benzoylecgonine ...

  • Simultaneous Determination of Heroin, 6-Monoacetylmorphine, Morphine, and its Glucuronides by Liquid Chromatography-Atmospheric Pressure Ionspray-Mass Spectrometry
    Journal of analytical toxicology, 1997
    Co-Authors: Piergiorgio Zuccaro, Simona Pichini, Roberta Pacifici, Manuela Pellegrini, R. Ricciarello, Ilaria Altieri, G. D'ascenzo
    Abstract:

    A new analytical technique has been developed for the simultaneous determination of heroin, 6-Monoacetylmorphine, morphine, morphine-6- and 3-glucuronides, and codeine in serum using liquid chromatography coupled with ionspray mass spectrometry. The analytes and the internal standard, nalorphine, were subjected to solid-phase extraction (SPE) using ethyl SPE columns before chromatography. The chromatographic separation of the analytes was achieved using a normal phase column and a water-methanol-acetonitrile-formic acid mobile phase at a flow rate of 230 microL/min. The mass spectrometer was operated in selected-ion monitoring mode. Under these conditions, the limit of quantitation was 0.5 ng/ml for heroin, 4 ng/ml for 6-Monoacetylmorphine, 4 ng/ml for morphine, 1 ng/ml for morphine-3-glucuronide, 4 ng/ml for morphine-6-glucuronide, and 4 ng/mL for codeine. Serum levels of heroin metabolites were determined in C57BL/6 inbred mice after a dose of 20 mg/kg heroin administered subcutaneously. 6-Monoacetylmorphine showed a peak concentration of 0.93 micrograms/mL serum at 3 min, whereas morphine and morphine-3-glucuronide achieved their peak concentrations of 9.6 and 2.9 micrograms/mL serum at 10 and 20 min, respectively. Finally, the absence of morphine-6-glucuronide and codeine excluded the possibility of their formation from morphine in this animal model.

Roberta Pacifici - One of the best experts on this subject based on the ideXlab platform.

  • Development and validation of a gas chromatography-mass spectrometry assay for opiates and cocaine in human teeth.
    Journal of pharmaceutical and biomedical analysis, 2005
    Co-Authors: Manuela Pellegrini, Roberta Pacifici, Emilia Marchei, Oscar Garcia-algar, Adriana Casá, Ruth Mayné, Vanessa Barbero, Simona Pichini
    Abstract:

    Abstract A procedure based on gas chromatography–mass spectrometry (GC–MS) is described for determination of opiates (6-Monoacetylmorphine, morphine and codeine) and cocaine and metabolites (cocaine, benzoylecgonine and cocaethylene) in human teeth. After addition of nalorphine as internal standard, pulverized samples were incubated in HCl at 37 °C for 18 h. Then, after pH adjustment to 6, and the analytes were extracted with two volumes of 3 ml of chloroform/isopropanol (9:1). Chromatography was performed on a fused silica capillary column and analytes were determined in the selected-ion-monitoring (SIM) mode. The assay was validated in the range 7.5 (6.0 in case of codeine) to 500 ng/g with mean absolute recoveries ranged between 74.1 and 92.1% for the different analytes and precision and accuracy always better than 15%. The method was applied to the analysis of teeth from drug-addicts to assess past chronic consumption and verify self-reported declarations. In case of opiates, concentration range was 36.5–570.0 ng/g for 6-Monoacetylmorphine, 8.7–154.8 ng/g for morphine and 7.9–127.9 ng/g for codeine. Cocaine concentration ranged between 5.6 and 57.2 ng/g with its principal metabolite benzoylecgonine varying from 12.6 to 81.7 ng/g and cocaethylene present in only one sample at 10 ng/g value. Teeth can be a promising non-invasive biological matrix in biomedical analysis for both clinical and forensic purposes.

  • Development and validation of a liquid chromatography-mass spectrometry assay for the determination of opiates and cocaine in meconium.
    Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2003
    Co-Authors: Simona Pichini, Roberta Pacifici, Manuela Pellegrini, Emilia Marchei, E. Perez-alarcòn, C. Puig, Oriol Vall, Oscar Garcia-algar
    Abstract:

    A procedure based on liquid chromatography-mass spectrometry (LC-MS) is described for determination of 6-Monoacetylmorphine, morphine, morphine-3-glucuronide, morphine-6-glucuronide, codeine, cocaine, benzoylecgonine and cocaethylene in meconium using nalorfine as the internal standard. The analytes are initially extracted from the matrix by methanol (6-Monoacetylmorphine, morphine, codeine, cocaine, benzoylecgonine and cocaethylene) or 0.01 M ammonium hydrogen carbonate buffer (morphine-3-glucuronide, morphine-6-glucuronide). Subsequently a solid-phase extraction with Bondelut Certify columns (6-Monoacetylmorphine, morphine, codeine, cocaine, benzoylecgonine and cocaethylene) or ethyl solid-phase extraction columns (morphine-3-glucuronide, morphine-6-glucuronide) was applied. Chromatography was performed on a C(8) reversed-phase column using a gradient of acetic acid 1%-acetonitrile as a mobile phase. Analytes were determined in LC-MS single ion monitoring mode with atmospheric pressure ionisation-electrospray (ESI) interface. The method was validated in the range 0.005-1.00 microg/g using 1 g of meconium per assay and applied to analysis of meconium in newborns to assess fetal exposure to opiates and cocaine.

  • Analysis of opiates in human hair by high-performance liquid chromatography
    Journal of Liquid Chromatography & Related Technologies, 1999
    Co-Authors: Simona Pichini, Roberta Pacifici, Manuela Pellegrini, Ilaria Altieri, Piergiorgio Zuccaro
    Abstract:

    A high-performance liquid chromatographic method with ultraviolet radiation absorbance detection has been developed for the determination of the principal opiates (heroin, 6-Monoacetylmorphine, morphine, codeine) in human hair. An amount of 100 mg hair was incubated with 2 mL HCl 0.1 M at 56°C overnight and it was then extracted by solid-phase extraction using reversed-phase/ion exchange cartridges. Chromatography has been performed using a C18 reversed-phase column with a mobile phase consisting of water-acetonitrile (70:30 v/v) containing 0.01 M NaH2PO4 and 0.002 M sodium laurylsulphate at a final pH of 2.1. The linearity of the method was obtained in the concentration range of 0.5-50 ng/mg hair for 6-Monoacetylmorphine, morphine and codeine, and of 5–200 ng/mg hair for heroin. The accuracy of the methodology was assessed using reference material from National Institute of Standards and Technology consisting of human hair segments and powdered human hair soaked with opiates. Cocaine and benzoylecgonine ...

  • Simultaneous Determination of Heroin, 6-Monoacetylmorphine, Morphine, and its Glucuronides by Liquid Chromatography-Atmospheric Pressure Ionspray-Mass Spectrometry
    Journal of analytical toxicology, 1997
    Co-Authors: Piergiorgio Zuccaro, Simona Pichini, Roberta Pacifici, Manuela Pellegrini, R. Ricciarello, Ilaria Altieri, G. D'ascenzo
    Abstract:

    A new analytical technique has been developed for the simultaneous determination of heroin, 6-Monoacetylmorphine, morphine, morphine-6- and 3-glucuronides, and codeine in serum using liquid chromatography coupled with ionspray mass spectrometry. The analytes and the internal standard, nalorphine, were subjected to solid-phase extraction (SPE) using ethyl SPE columns before chromatography. The chromatographic separation of the analytes was achieved using a normal phase column and a water-methanol-acetonitrile-formic acid mobile phase at a flow rate of 230 microL/min. The mass spectrometer was operated in selected-ion monitoring mode. Under these conditions, the limit of quantitation was 0.5 ng/ml for heroin, 4 ng/ml for 6-Monoacetylmorphine, 4 ng/ml for morphine, 1 ng/ml for morphine-3-glucuronide, 4 ng/ml for morphine-6-glucuronide, and 4 ng/mL for codeine. Serum levels of heroin metabolites were determined in C57BL/6 inbred mice after a dose of 20 mg/kg heroin administered subcutaneously. 6-Monoacetylmorphine showed a peak concentration of 0.93 micrograms/mL serum at 3 min, whereas morphine and morphine-3-glucuronide achieved their peak concentrations of 9.6 and 2.9 micrograms/mL serum at 10 and 20 min, respectively. Finally, the absence of morphine-6-glucuronide and codeine excluded the possibility of their formation from morphine in this animal model.

James M. Fujimoto - One of the best experts on this subject based on the ideXlab platform.

  • Morphine Tolerance in Mice Changes Response of Heroin from μ to δ Opioid Receptors
    Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York N.Y.), 2008
    Co-Authors: Jodie J. Rady, Blythe B. Holmes, Philip S. Portoghese, James M. Fujimoto
    Abstract:

    Heroin produced antinociception in the tail flick test through mu receptors in the brain of ICR and CD-1 mice, a response inhibited by 3-O-methylnaltrexone. Tolerance to morphine was produced by subcutaneous morphine pellet implantation. By the third day, the heroin response was produced through delta opioid receptors. The response was inhibited by simultaneous intracerebroventricular (i.c. v.) administration of naltrindole, a delta opioid receptor antagonist. More specifically, delta1 rather than delta2 receptors were involved because 7-benzylidenenaltrexone, a delta1 receptor antagonist, inhibited but naltriben, a delta2 antagonist, did not. Also, antinociception produced by i.c.v. heroin was inhibited by intrathecal administration of bicuculline and picrotoxin consistent with the concept that delta1 receptors in the brain mediated the antinociceptive response through descending neuronal pathways to the spinal cord to activate GABAA and GABAB receptors rather than spinal alpha2-adrenergic and serotonergic receptors activated originally by the mu agonist action in naive mice. The mu response of 6-Monoacetylmorphine, a metabolite of heroin, was changed by morphine pellet implantation to a delta2 response (inhibited by naltriben but not 7-benzylidenenaltrexone). The agonist action of morphine in these morphine-tolerant mice remained mu. Thus, the opioid receptor selectivity of heroin and 6-Monoacetylmorphine in the brain is changed by production of tolerance to morphine. Such a change explains how morphine tolerant mice are not cross-tolerant to heroin.

  • Acute cross-tolerance to opioids in heroin delta-opioid-responding Swiss Webster mice.
    Journal of biomedical science, 2000
    Co-Authors: Jodie J. Rady, James M. Fujimoto
    Abstract:

    It is generally thought that the μ receptor actions of metabolites, 6-Monoacetylmorphine (6MAM) and morphine, account for the pharmacological actions of heroin. However, upon intracerebroventricular (

  • Spinal delta opioid receptor subtype activity of 6-Monoacetylmorphine in Swiss Webster mice.
    Pharmacology biochemistry and behavior, 1997
    Co-Authors: Jodie J. Rady, Philip S. Portoghese, Daniel Baemmert, A. E. Takemori, James M. Fujimoto
    Abstract:

    Abstract Heroin and 6-Monoacetylmorphine (6MAM) given intracerebroventricularly in Swiss Webster mice, act on supraspinal delta (δ) opioid receptors to produce antinociception in the tail flick test. More specifically, this action of heroin involves δ1 and 6MAM involves δ2 opioid receptors. Even though 6MAM given intrathecally (IT) in Swiss Webster mice also activates δ receptors to produce antinociception, the subtype of δ receptor in the spinal cord is not known. The present study addressed this question. First, in order to confirm the subtype selectivity of the δ opioid receptor antagonists in the spinal cord, 7-benzylidenenaltrexone (BNTX, a selective δ1 receptor antagonist) and naltriben (a selective δ2 receptor antagonist) were administered IT against the prototypic δ1 and δ2 peptide agonists [D-Pen2,5]enkephalin (DPDPE) and [D-Ser2,Leu5]enkephalin-Thr (DSLET), respectively. DPDPE-induced antinociception was inhibited by BNTX, but not naltriben. The opposite selectivity occurred for DSLET; naltriben, but not BNTX, administered IT inhibited IT DSLET-induced antinociception. Therefore, the antagonists differentiated between spinal δ1 and δ2 opioid receptor subtype agonist actions. This differentiation was further demonstrated by administration of the antagonists IT against the antinociceptive action of β-endorphin given intracerebroventricularly. The antinociceptive action of β-endorphin is due to spinal release of met-enkephalin which results in spinal δ2 receptor activation. This antinociception was reduced by IT naltriben, but not BNTX, administration. The antagonists were then administered against IT 6MAM-induced antinociception. Neither BNTX nor naltriben given alone, each at twice the usual dose, altered IT 6MAM-induced antinociception. When the antagonists were administered together, each at the usual dose, the antinociceptive action of 6MAM was inhibited. Thus, even though a differentiation between spinal δ1 and δ2 opioid receptor activity can be obtained with naltriben and BNTX, blockade of the individual δ receptor subtypes does not appear to alter IT 6MAM antinociception. Therefore, these results suggest that 6MAM, given IT, is acting on a δ opioid receptor but this receptor in the spinal cord appears to be different from the δ2 receptor on which 6MAM acts in the brain.

  • Supraspinal delta2 opioid agonist analgesia in Swiss-Webster mice involves spinal GABAA receptors
    Pharmacology biochemistry and behavior, 1996
    Co-Authors: Jodie J. Rady, James M. Fujimoto
    Abstract:

    The tail-flick response is a spinal reflex that can be modulated by administration of antinociceptive agents supraspinally through activation of descending systems and involvement of the action of neurotransmitters in the spinal cord. Descending noradrenergic and serotonergic systems are involved in morphine (and other μ opioid receptor agonists)-induced antinociception. These descending systems, however, are not involved in supraspinal δ opioid receptor agonist-induced antinociception. Recently, a descending system mediated by spinal gamma-aminobutyric acid (GABA) A and B receptors has been demonstrated to be involved in the antinociceptive action of δ1 opioid receptor agonists ([D-Pen2,5]enkephalin in ICR mice and [D-Pen2,5]enkephalin and heroin in Swiss-Webster mice). In the present study, the involvement of spinal GABAA receptors in the antinociceptive action of supraspinal δ2 opioid receptor agonists, [D-Ser2]-Leu-enkephalin-Thr and 6-Monoacetylmorphine, action was demonstrated. The intrathecal administration of GABAA receptor antagonists, bicuculline and picrotoxin, inhibited the antinociceptive action of both [D-Ser2]-Leu-enkephalin-Thr and 6-Monoacetylmorphine given intracerebroventricularly. The intrathecal administration of 2-hydroxysaclofen, a GABAB receptor antagonist, had no effect. These studies suggest that supraspinal δ2 like δ1, opioid receptor action involves spinal GABAA receptors, but δ2, unlike δ2, action does not involve GABAB receptors. Thus, the supraspinal δ1 agonist action (heroin, DPDPE) and the δ2 agonist action (6MAM, DSLET) can be further differentiated by the selectivity of the spinal GABA receptors involved in Swiss-Webster mice.

  • Supraspinal delta receptor subtype activity of heroin and 6-Monoacetylmorphine in Swiss webster mice
    Life sciences, 1994
    Co-Authors: Jodie J. Rady, Philip S. Portoghese, A. E. Takemori, James M. Fujimoto
    Abstract:

    The purpose of this study was to determine which delta (delta) opioid receptor subtype, delta 1 or delta 2, was involved in producing the antinociceptive action of heroin and 6-monacetylmorphine (MAM) in Swiss Webster mice. Previous work from this laboratory established that heroin and MAM, given intracerebroventricularly (i.c.v.) in Swiss Webster mice, produce antinociception through activation of supraspinal delta receptors. Naltrindole, but not naloxone or nor-binaltorphimine, antagonizes the inhibitory action of heroin and MAM in the tail-flick test. Recent literature documents the occurrence of subtypes of the delta opioid receptor and the availability of selective antagonists. 7-Benzylidenenaltrexone (BNTX) antagonizes the antinociception induced by delta 1 receptor agonists without affecting that induced by delta 2 receptor agonists. Naltriben (NTB) selectively inhibits delta 2- but not delta 1-induced antinociception. In the present study BNTX and NTB were administered i.c.v. with heroin and MAM to determine the delta receptor subtype responsible for inhibition of the tail-flick response in Swiss Webster mice. The ED50 for heroin-induced antinociception was increased 19-fold by BNTX and was not altered by NTB administration. On the other hand, the ED50 value of MAM was increased 3-fold by NTB and was not altered by BNTX administration. These results suggest that heroin activated supraspinal delta 1 receptors and MAM acted on supraspinal delta 2 receptors to produce antinociception in Swiss Webster mice.

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