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Matthew L Banks - One of the best experts on this subject based on the ideXlab platform.
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dissociable effects of the prodrug Phendimetrazine and its metabolite phenmetrazine at dopamine transporters
Scientific Reports, 2016Co-Authors: Ernesto Solis, Bruce E. Blough, Stevens S Negus, Julie A Suyama, Matthew F Lazenka, Louis J Defelice, Matthew L BanksAbstract:Phendimetrazine (PDM) is a clinically available anorectic and a candidate pharmacotherapy for cocaine addiction. PDM has been hypothesized to function as a prodrug that requires metabolism to the amphetamine-like monoamine transporter substrate phenmetrazine (PM) to produce its pharmacological effects; however, whether PDM functions as an inactive prodrug or has pharmacological activity on its own remains unclear. The study aim was to determine PDM pharmacological mechanisms using electrophysiological, neurochemical, and behavioral procedures. PDM blocked the endogenous basal hDAT (human dopamine transporter) current in voltage-clamped (−60 mV) oocytes consistent with a DAT inhibitor profile, whereas its metabolite PM induced an inward hDAT current consistent with a DAT substrate profile. PDM also attenuated the PM-induced inward current during co-application, providing further evidence that PDM functions as a DAT inhibitor. PDM increased nucleus accumbens dopamine levels and facilitated electrical brain stimulation reinforcement within 10 min in rats, providing in vivo evidence supporting PDM pharmacological activity. These results demonstrate that PDM functions as a DAT inhibitor that may also interact with the pharmacological effects of its metabolite PM. Overall, these results suggest a novel mechanism for PDM therapeutic effects via initial PDM DAT inhibition followed by PM DAT substrate-induced dopamine release.
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cocaine like discriminative stimulus effects of Phendimetrazine and phenmetrazine in rats
Behavioural Pharmacology, 2016Co-Authors: Clayton T Bauer, Bruce E. Blough, Stevens S Negus, Matthew L BanksAbstract:Phendimetrazine is a clinically available anorectic and candidate medication for the treatment of cocaine addiction. Phendimetrazine can be metabolized to the amphetamine-like monoamine releaser phenmetrazine, but it is unclear if Phendimetrazine functions as an inactive prodrug or might have activity on its own. As one method to address this issue, the present study compared the potency and time course of Phendimetrazine and phenmetrazine to produce cocaine-like discriminative stimulus effects in adult, male rats (N=5) trained to discriminate cocaine (5.6 mg/kg, intraperitoneally) from saline in a two-key food-reinforced discrimination procedure. We hypothesized that, if metabolism to phenmetrazine was required for Phendimetrazine effects, then Phendimetrazine would be less potent and have a slower onset and offset of effects than phenmetrazine. Both Phendimetrazine and phenmetrazine produced dose-dependent cocaine-like discriminative stimulus effects, and Phendimetrazine was 7.8-fold less potent than phenmetrazine. However, the time courses of discriminative stimulus effects produced by Phendimetrazine and phenmetrazine were similar, with peak effects at 10 min and offset by 100 min. These results show the effectiveness of Phendimetrazine to rapidly produce cocaine-like behavioral effects in rats and support other nonhuman primate evidence to suggest that metabolism to phenmetrazine may not be required for Phendimetrazine effects.
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a generalized matching law analysis of cocaine vs food choice in rhesus monkeys effects of candidate agonist based medications on sensitivity to reinforcement
Drug and Alcohol Dependence, 2015Co-Authors: Blake A Hutsell, Stevens S Negus, Matthew L BanksAbstract:Abstract Background We have previously demonstrated reductions in cocaine choice produced by either continuous 14-day Phendimetrazine and d -amphetamine treatment or removing cocaine availability under a cocaine vs. food choice procedure in rhesus monkeys. The aim of the present investigation was to apply the concatenated generalized matching law (GML) to cocaine vs. food choice dose-effect functions incorporating sensitivity to both the relative magnitude and price of each reinforcer. Our goal was to determine potential behavioral mechanisms underlying pharmacological treatment efficacy to decrease cocaine choice. Methods A multi-model comparison approach was used to characterize dose- and time-course effects of both pharmacological and environmental manipulations on sensitivity to reinforcement. Results GML models provided an excellent fit of the cocaine choice dose-effect functions in individual monkeys. Reductions in cocaine choice by both pharmacological and environmental manipulations were principally produced by systematic decreases in sensitivity to reinforcer price and non-systematic changes in sensitivity to reinforcer magnitude. Conclusions The modeling approach used provides a theoretical link between the experimental analysis of choice and pharmacological treatments being evaluated as candidate ‘agonist-based’ medications for cocaine addiction. The analysis suggests that monoamine releaser treatment efficacy to decrease cocaine choice was mediated by selectively increasing the relative price of cocaine. Overall, the net behavioral effect of these pharmacological treatments was to increase substitutability of food pellets, a nondrug reinforcer, for cocaine.
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effects of 14 day treatment with the schedule iii anorectic Phendimetrazine on choice between cocaine and food in rhesus monkeys
Drug and Alcohol Dependence, 2013Co-Authors: Matthew L Banks, Bruce E. Blough, Stevens S NegusAbstract:Abstract Background The clinical utility of monoamine releasers such as phenmetrazine or d-amphetamine as candidate agonist medications for cocaine dependence is hindered by their high abuse liability. Phendimetrazine is a clinically available schedule III anorectic that functions as a prodrug for phenmetrazine and thus may have lower abuse liability. This study determined the effects of continuous 14-day treatment with Phendimetrazine on cocaine vs. food choice in rhesus monkeys (N = 4). Methods Responding was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and cocaine injections (0–0.1 mg/kg/injection, fixed-ratio 10 schedule). Cocaine choice dose–effect curves were determined daily before and during 14-day periods of continuous intravenous treatment with saline or (+)-Phendimetrazine (0.32–1.0 mg/kg/h). Effects of 14-day treatment with (+)-phenmetrazine (0.1–0.32 mg/kg/h; N = 5) and d-amphetamine (0.032–0.1 mg/kg/h; N = 6) were also examined for comparison. Results During saline treatment, food was primarily chosen during availability of low cocaine doses (0, 0.0032, and 0.01 mg/kg/injection), and cocaine was primarily chosen during availability of higher cocaine doses (0.032 and 0.1 mg/kg/injection). Phendimetrazine initially decreased overall responding without significantly altering cocaine choice. Over the course of 14 days, tolerance developed to rate decreasing effects, and Phendimetrazine dose-dependently decreased cocaine choice (significant at 0.032 mg/kg/injection cocaine). Phenmetrazine and d-amphetamine produced qualitatively similar effects. Conclusions These results demonstrate that Phendimetrazine can produce significant, though modest, reductions in cocaine choice in rhesus monkeys. Phendimetrazine may be especially suitable as a candidate medication for human studies because of its schedule III clinical availability.
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role of phenmetrazine as an active metabolite of Phendimetrazine evidence from studies of drug discrimination and pharmacokinetics in rhesus monkeys
Drug and Alcohol Dependence, 2013Co-Authors: Matthew L Banks, Bruce E. Blough, Timothy R Fennell, Rodney W Snyder, Stevens S NegusAbstract:Background Monoamine releasers such as d-amphetamine that selectively promote release of dopamine/norepinephrine versus serotonin are one class of candidate medications for treating cocaine dependence; however, their clinical utility is limited by undesirable effects such as abuse liability. Clinical utility of these compounds may be increased by development of prodrugs to reduce abuse potential by slowing onset of drug effects. This study examined the behavioral and pharmacokinetic profile of the Schedule III compound Phendimetrazine, which may serve as a prodrug for the N-demethylated metabolite and potent dopamine/norepinephrine releaser phenmetrazine.
Stevens S Negus - One of the best experts on this subject based on the ideXlab platform.
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dissociable effects of the prodrug Phendimetrazine and its metabolite phenmetrazine at dopamine transporters
Scientific Reports, 2016Co-Authors: Ernesto Solis, Bruce E. Blough, Stevens S Negus, Julie A Suyama, Matthew F Lazenka, Louis J Defelice, Matthew L BanksAbstract:Phendimetrazine (PDM) is a clinically available anorectic and a candidate pharmacotherapy for cocaine addiction. PDM has been hypothesized to function as a prodrug that requires metabolism to the amphetamine-like monoamine transporter substrate phenmetrazine (PM) to produce its pharmacological effects; however, whether PDM functions as an inactive prodrug or has pharmacological activity on its own remains unclear. The study aim was to determine PDM pharmacological mechanisms using electrophysiological, neurochemical, and behavioral procedures. PDM blocked the endogenous basal hDAT (human dopamine transporter) current in voltage-clamped (−60 mV) oocytes consistent with a DAT inhibitor profile, whereas its metabolite PM induced an inward hDAT current consistent with a DAT substrate profile. PDM also attenuated the PM-induced inward current during co-application, providing further evidence that PDM functions as a DAT inhibitor. PDM increased nucleus accumbens dopamine levels and facilitated electrical brain stimulation reinforcement within 10 min in rats, providing in vivo evidence supporting PDM pharmacological activity. These results demonstrate that PDM functions as a DAT inhibitor that may also interact with the pharmacological effects of its metabolite PM. Overall, these results suggest a novel mechanism for PDM therapeutic effects via initial PDM DAT inhibition followed by PM DAT substrate-induced dopamine release.
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cocaine like discriminative stimulus effects of Phendimetrazine and phenmetrazine in rats
Behavioural Pharmacology, 2016Co-Authors: Clayton T Bauer, Bruce E. Blough, Stevens S Negus, Matthew L BanksAbstract:Phendimetrazine is a clinically available anorectic and candidate medication for the treatment of cocaine addiction. Phendimetrazine can be metabolized to the amphetamine-like monoamine releaser phenmetrazine, but it is unclear if Phendimetrazine functions as an inactive prodrug or might have activity on its own. As one method to address this issue, the present study compared the potency and time course of Phendimetrazine and phenmetrazine to produce cocaine-like discriminative stimulus effects in adult, male rats (N=5) trained to discriminate cocaine (5.6 mg/kg, intraperitoneally) from saline in a two-key food-reinforced discrimination procedure. We hypothesized that, if metabolism to phenmetrazine was required for Phendimetrazine effects, then Phendimetrazine would be less potent and have a slower onset and offset of effects than phenmetrazine. Both Phendimetrazine and phenmetrazine produced dose-dependent cocaine-like discriminative stimulus effects, and Phendimetrazine was 7.8-fold less potent than phenmetrazine. However, the time courses of discriminative stimulus effects produced by Phendimetrazine and phenmetrazine were similar, with peak effects at 10 min and offset by 100 min. These results show the effectiveness of Phendimetrazine to rapidly produce cocaine-like behavioral effects in rats and support other nonhuman primate evidence to suggest that metabolism to phenmetrazine may not be required for Phendimetrazine effects.
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a generalized matching law analysis of cocaine vs food choice in rhesus monkeys effects of candidate agonist based medications on sensitivity to reinforcement
Drug and Alcohol Dependence, 2015Co-Authors: Blake A Hutsell, Stevens S Negus, Matthew L BanksAbstract:Abstract Background We have previously demonstrated reductions in cocaine choice produced by either continuous 14-day Phendimetrazine and d -amphetamine treatment or removing cocaine availability under a cocaine vs. food choice procedure in rhesus monkeys. The aim of the present investigation was to apply the concatenated generalized matching law (GML) to cocaine vs. food choice dose-effect functions incorporating sensitivity to both the relative magnitude and price of each reinforcer. Our goal was to determine potential behavioral mechanisms underlying pharmacological treatment efficacy to decrease cocaine choice. Methods A multi-model comparison approach was used to characterize dose- and time-course effects of both pharmacological and environmental manipulations on sensitivity to reinforcement. Results GML models provided an excellent fit of the cocaine choice dose-effect functions in individual monkeys. Reductions in cocaine choice by both pharmacological and environmental manipulations were principally produced by systematic decreases in sensitivity to reinforcer price and non-systematic changes in sensitivity to reinforcer magnitude. Conclusions The modeling approach used provides a theoretical link between the experimental analysis of choice and pharmacological treatments being evaluated as candidate ‘agonist-based’ medications for cocaine addiction. The analysis suggests that monoamine releaser treatment efficacy to decrease cocaine choice was mediated by selectively increasing the relative price of cocaine. Overall, the net behavioral effect of these pharmacological treatments was to increase substitutability of food pellets, a nondrug reinforcer, for cocaine.
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effects of 14 day treatment with the schedule iii anorectic Phendimetrazine on choice between cocaine and food in rhesus monkeys
Drug and Alcohol Dependence, 2013Co-Authors: Matthew L Banks, Bruce E. Blough, Stevens S NegusAbstract:Abstract Background The clinical utility of monoamine releasers such as phenmetrazine or d-amphetamine as candidate agonist medications for cocaine dependence is hindered by their high abuse liability. Phendimetrazine is a clinically available schedule III anorectic that functions as a prodrug for phenmetrazine and thus may have lower abuse liability. This study determined the effects of continuous 14-day treatment with Phendimetrazine on cocaine vs. food choice in rhesus monkeys (N = 4). Methods Responding was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and cocaine injections (0–0.1 mg/kg/injection, fixed-ratio 10 schedule). Cocaine choice dose–effect curves were determined daily before and during 14-day periods of continuous intravenous treatment with saline or (+)-Phendimetrazine (0.32–1.0 mg/kg/h). Effects of 14-day treatment with (+)-phenmetrazine (0.1–0.32 mg/kg/h; N = 5) and d-amphetamine (0.032–0.1 mg/kg/h; N = 6) were also examined for comparison. Results During saline treatment, food was primarily chosen during availability of low cocaine doses (0, 0.0032, and 0.01 mg/kg/injection), and cocaine was primarily chosen during availability of higher cocaine doses (0.032 and 0.1 mg/kg/injection). Phendimetrazine initially decreased overall responding without significantly altering cocaine choice. Over the course of 14 days, tolerance developed to rate decreasing effects, and Phendimetrazine dose-dependently decreased cocaine choice (significant at 0.032 mg/kg/injection cocaine). Phenmetrazine and d-amphetamine produced qualitatively similar effects. Conclusions These results demonstrate that Phendimetrazine can produce significant, though modest, reductions in cocaine choice in rhesus monkeys. Phendimetrazine may be especially suitable as a candidate medication for human studies because of its schedule III clinical availability.
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role of phenmetrazine as an active metabolite of Phendimetrazine evidence from studies of drug discrimination and pharmacokinetics in rhesus monkeys
Drug and Alcohol Dependence, 2013Co-Authors: Matthew L Banks, Bruce E. Blough, Timothy R Fennell, Rodney W Snyder, Stevens S NegusAbstract:Background Monoamine releasers such as d-amphetamine that selectively promote release of dopamine/norepinephrine versus serotonin are one class of candidate medications for treating cocaine dependence; however, their clinical utility is limited by undesirable effects such as abuse liability. Clinical utility of these compounds may be increased by development of prodrugs to reduce abuse potential by slowing onset of drug effects. This study examined the behavioral and pharmacokinetic profile of the Schedule III compound Phendimetrazine, which may serve as a prodrug for the N-demethylated metabolite and potent dopamine/norepinephrine releaser phenmetrazine.
Bruce E. Blough - One of the best experts on this subject based on the ideXlab platform.
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dissociable effects of the prodrug Phendimetrazine and its metabolite phenmetrazine at dopamine transporters
Scientific Reports, 2016Co-Authors: Ernesto Solis, Bruce E. Blough, Stevens S Negus, Julie A Suyama, Matthew F Lazenka, Louis J Defelice, Matthew L BanksAbstract:Phendimetrazine (PDM) is a clinically available anorectic and a candidate pharmacotherapy for cocaine addiction. PDM has been hypothesized to function as a prodrug that requires metabolism to the amphetamine-like monoamine transporter substrate phenmetrazine (PM) to produce its pharmacological effects; however, whether PDM functions as an inactive prodrug or has pharmacological activity on its own remains unclear. The study aim was to determine PDM pharmacological mechanisms using electrophysiological, neurochemical, and behavioral procedures. PDM blocked the endogenous basal hDAT (human dopamine transporter) current in voltage-clamped (−60 mV) oocytes consistent with a DAT inhibitor profile, whereas its metabolite PM induced an inward hDAT current consistent with a DAT substrate profile. PDM also attenuated the PM-induced inward current during co-application, providing further evidence that PDM functions as a DAT inhibitor. PDM increased nucleus accumbens dopamine levels and facilitated electrical brain stimulation reinforcement within 10 min in rats, providing in vivo evidence supporting PDM pharmacological activity. These results demonstrate that PDM functions as a DAT inhibitor that may also interact with the pharmacological effects of its metabolite PM. Overall, these results suggest a novel mechanism for PDM therapeutic effects via initial PDM DAT inhibition followed by PM DAT substrate-induced dopamine release.
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cocaine like discriminative stimulus effects of Phendimetrazine and phenmetrazine in rats
Behavioural Pharmacology, 2016Co-Authors: Clayton T Bauer, Bruce E. Blough, Stevens S Negus, Matthew L BanksAbstract:Phendimetrazine is a clinically available anorectic and candidate medication for the treatment of cocaine addiction. Phendimetrazine can be metabolized to the amphetamine-like monoamine releaser phenmetrazine, but it is unclear if Phendimetrazine functions as an inactive prodrug or might have activity on its own. As one method to address this issue, the present study compared the potency and time course of Phendimetrazine and phenmetrazine to produce cocaine-like discriminative stimulus effects in adult, male rats (N=5) trained to discriminate cocaine (5.6 mg/kg, intraperitoneally) from saline in a two-key food-reinforced discrimination procedure. We hypothesized that, if metabolism to phenmetrazine was required for Phendimetrazine effects, then Phendimetrazine would be less potent and have a slower onset and offset of effects than phenmetrazine. Both Phendimetrazine and phenmetrazine produced dose-dependent cocaine-like discriminative stimulus effects, and Phendimetrazine was 7.8-fold less potent than phenmetrazine. However, the time courses of discriminative stimulus effects produced by Phendimetrazine and phenmetrazine were similar, with peak effects at 10 min and offset by 100 min. These results show the effectiveness of Phendimetrazine to rapidly produce cocaine-like behavioral effects in rats and support other nonhuman primate evidence to suggest that metabolism to phenmetrazine may not be required for Phendimetrazine effects.
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effects of 14 day treatment with the schedule iii anorectic Phendimetrazine on choice between cocaine and food in rhesus monkeys
Drug and Alcohol Dependence, 2013Co-Authors: Matthew L Banks, Bruce E. Blough, Stevens S NegusAbstract:Abstract Background The clinical utility of monoamine releasers such as phenmetrazine or d-amphetamine as candidate agonist medications for cocaine dependence is hindered by their high abuse liability. Phendimetrazine is a clinically available schedule III anorectic that functions as a prodrug for phenmetrazine and thus may have lower abuse liability. This study determined the effects of continuous 14-day treatment with Phendimetrazine on cocaine vs. food choice in rhesus monkeys (N = 4). Methods Responding was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and cocaine injections (0–0.1 mg/kg/injection, fixed-ratio 10 schedule). Cocaine choice dose–effect curves were determined daily before and during 14-day periods of continuous intravenous treatment with saline or (+)-Phendimetrazine (0.32–1.0 mg/kg/h). Effects of 14-day treatment with (+)-phenmetrazine (0.1–0.32 mg/kg/h; N = 5) and d-amphetamine (0.032–0.1 mg/kg/h; N = 6) were also examined for comparison. Results During saline treatment, food was primarily chosen during availability of low cocaine doses (0, 0.0032, and 0.01 mg/kg/injection), and cocaine was primarily chosen during availability of higher cocaine doses (0.032 and 0.1 mg/kg/injection). Phendimetrazine initially decreased overall responding without significantly altering cocaine choice. Over the course of 14 days, tolerance developed to rate decreasing effects, and Phendimetrazine dose-dependently decreased cocaine choice (significant at 0.032 mg/kg/injection cocaine). Phenmetrazine and d-amphetamine produced qualitatively similar effects. Conclusions These results demonstrate that Phendimetrazine can produce significant, though modest, reductions in cocaine choice in rhesus monkeys. Phendimetrazine may be especially suitable as a candidate medication for human studies because of its schedule III clinical availability.
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role of phenmetrazine as an active metabolite of Phendimetrazine evidence from studies of drug discrimination and pharmacokinetics in rhesus monkeys
Drug and Alcohol Dependence, 2013Co-Authors: Matthew L Banks, Bruce E. Blough, Timothy R Fennell, Rodney W Snyder, Stevens S NegusAbstract:Background Monoamine releasers such as d-amphetamine that selectively promote release of dopamine/norepinephrine versus serotonin are one class of candidate medications for treating cocaine dependence; however, their clinical utility is limited by undesirable effects such as abuse liability. Clinical utility of these compounds may be increased by development of prodrugs to reduce abuse potential by slowing onset of drug effects. This study examined the behavioral and pharmacokinetic profile of the Schedule III compound Phendimetrazine, which may serve as a prodrug for the N-demethylated metabolite and potent dopamine/norepinephrine releaser phenmetrazine.
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interaction of the anorectic medication Phendimetrazine and its metabolites with monoamine transporters in rat brain
European Journal of Pharmacology, 2002Co-Authors: Richard B. Rothman, Bruce E. Blough, Marina Katsnelson, John S Partilla, Christina M Dersch, Michael H. BaumannAbstract:Abstract Phendimetrazine is an effective and widely prescribed appetite suppressant. Preclinical findings show that Phendimetrazine displays stimulant properties similar to amphetamine, but few studies have examined the neurochemical mechanism of the drug. In the present work, we characterize the activity of Phendimetrazine and its putative metabolites [phenmetrazine, pseudophenmetrazine, and associated stereoisomers] at biogenic amine transporters. All drugs were tested in vitro using assays to measure uptake and release of [ 3 H]dopamine, [ 3 H]norepinephrine, and [ 3 H]serotonin ([ 3 H]5-HT) in rat brain synaptosomes. Selected drugs were tested in vivo using microdialysis to measure extracellular dopamine and serotonin (5-HT) in rat nucleus accumbens. Phendimetrazine itself had no effect on uptake or release of any transmitter. In contrast, the trans -configured N -demethylated metabolite, phenmetrazine, was a potent releaser of [ 3 H]norepinephrine (EC 50 =50 nM) and [ 3 H]dopamine (EC 50 =131 nM). The cis N -demethylated metabolite, pseudophenmetrazine, displayed modest potency at releasing [ 3 H]norepinephrine (EC 50 =514 nM) and blocking [ 3 H]dopamine re-uptake (IC 50 =2630 nM). All drugs tested were inactive or weak in the [ 3 H]5-HT assays. When injected intravenously, Phendimetrazine had minimal effects on extracellular transmitter levels, whereas phenmetrazine produced dose-related elevations in extracellular dopamine. The collective findings suggest that Phendimetrazine is a “prodrug” that is converted to the active metabolite phenmetrazine, a potent substrate for norepinephrine and dopamine transporters.
Rosalyn Middleton - One of the best experts on this subject based on the ideXlab platform.
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GC-MS Identification of Sympathomimetic Amine Drugs in Urine: Rapid Methodology Applicable for Emergency Clinical Toxicology
2016Co-Authors: Jimmie L Valentine, Rosalyn MiddletonAbstract:A method was developed that permitted rapid identification in urine of the following sympathomimetic amines: amphetamine, benzphetamine, cathinone, desmethylsegiline, diethylpropion, ephedrine, fenfluramine, mazindol, methylenedioxyamphetamine, methylenedioxyethylamphetamine, ethylenedioxymethamphetamine, mescaline, methamphetamine, methcathinone, methylaminorex, methylphenidate, pemoline, Phendimetrazine, phenylepherine, phentermine, phenylpropanolamine, pseudoephedrine, and selegiline. In addition, two c~-phenylethylamine-like monoamine oxidase inhibitors, phenelizine and tranylcypromine, were studied. Those sympathomimetic amines containing a primary o secondary amine, a hydrazine, and/or hydroxyl (except mazindol) functional groups were derivatized effectively using an on-column derivatization technique that used a reagent consisting of 10
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gc ms identification of sympathomimetic amine drugs in urine rapid methodology applicable for emergency clinical toxicology
Journal of Analytical Toxicology, 2000Co-Authors: Jimmie L Valentine, Rosalyn MiddletonAbstract:A method was developed that permitted rapid identification in urine of the following sympathomimetic amines: amphetamine, benzphetamine, cathinone, desmethylsegiline, diethylpropion, ephedrine, fenfluramine, mazindol, methylenedioxyamphetamine, methylenedioxyethylamphetamine, methylenedioxymethamphetamine, mescaline, methamphetamine, methcathinone, methylaminorex, methylphenidate, pemoline, Phendimetrazine, phenylepherine, phentermine, phenylpropanolamine, and selegiline. In two c~-phenylethylamine-like monoamine oxidase inhibitors, phenelizine and tranylcypromine, were studied. Those sympathomimetic amines containing a primary or secondary amine, a hydrazine, and/or hydroxyl (except mazindol) functional groups were derivatized effectively using an on-column derivatization technique that used a reagent consisting of 10% fluoroanhydride in hexane, whereas the other sympathomimetic amines, including mazindol, were analyzed underivatized. Three different fluoroanhydrides, trifluoroacetic (TFAA), pentafluoropropionic (PFPA), and heptafluorobutyric (HFBA), and three different injection-port temperatures (160, 200, and 260~ were investigated. Both TFAA and PFPA gave sympathomimetic amine derivatives with essentially identical retention times, whereas HFBA gave longer retention times and better separation of individual compounds. The base fragmentation ion was noted to increase 50 ainu (CF~) for each derivatized sympathomimetic amine as the length of the carbon-fluorine chain increased. Fragmentation ion abundance was maximized at injection-port temperature of 260~ and this enhanced sensitivity coupled with the better chromatographic resolution of the individual sympathomimetic amines prompted the selection of HFBA as the derivatizing agent of choice. Assignments were made for the fragmentation ions produced by each derivatized drug. The developed method was adapted to analyze urine specimens that might be encountered in emergency toxicology testing. For identification of sympathomimetic
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gc ms identification of sympathomimetic amine drugs in urine rapid methodology applicable for emergency clinical toxicology
Journal of Analytical Toxicology, 2000Co-Authors: Jimmie L Valentine, Rosalyn MiddletonAbstract:A method was developed that permitted rapid identification in urine of the following sympathomimetic amines: amphetamine, benzphetamine, cathinone, desmethylsegiline, diethylpropion, ephedrine, fenfluramine, mazindol, methylenedioxyamphetamine, methylenedioxyethylamphetamine, methylenedioxymethamphetamine, mescaline, methamphetamine, methcathinone, methylaminorex, methylphenidate, pemoline, Phendimetrazine, phenylepherine, phentermine, phenylpropanolamine, pseudoephedrine, and selegiline. In addition, two alpha-phenylethylamine-like monoamine oxidase inhibitors, phenelizine and tranylcypromine, were studied. Those sympathomimetic amines containing a primary or secondary amine, a hydrazine, and/or hydroxyl (except mazindol) functional groups were derivatized effectively using an on-column derivatization technique that used a reagent consisting of 10% fluoroanhydride in hexane, whereas the other sympathomimetic amines, including mazindol, were analyzed underivatized. Three different fluoroanhydrides, trifluoroacetic (TFAA), pentafluoropropionic (PFPA), and heptafluorobutyric (HFBA), and three different injection-port temperatures (160, 200, and 260 degrees C) were investigated. Both TFAA and PFPA gave sympathomimetic amine derivatives with essentially identical retention times, whereas HFBA gave longer retention times and better separation of individual compounds. The base fragmentation ion was noted to increase 50 amu (CF2) for each derivatized sympathomimetic amine as the length of the carbon-fluorine chain increased. Fragmentation ion abundance was maximized at an injection-port temperature of 260 degrees C, and this enhanced sensitivity coupled with the better chromatographic resolution of the individual sympathomimetic amines prompted the selection of HFBA as the derivatizing agent of choice. Assignments were made for the fragmentation ions produced by each derivatized drug. The developed method was adapted to analyze urine specimens that might be encountered in emergency toxicology testing. For identification of sympathomimetic amines requiring derivatization, 0.1 mL of the patient specimen had amphetamine-d5 and methamphetamine-d5 added as internal standard followed by adjustment of pH to 9.3 with borate buffer, extraction with 9:1 chloroform/isopropanol, centrifugation and separation of the organic phase, addition of 10% methanolic HCI and evaporation under nitrogen, reconstitution with HFBA reagent, and on-column derivatization during gas chromatographic-mass spectrometric (GC-MS) analysis. For those sympathomimetic amines not requiring derivatization, 1.0 mL of urine specimen had diazepam-d5 added as internal standard followed by the same extraction procedure and reconstitution accomplished with ethyl acetate. Because precolumn derivatization was eliminated and only 8 min was required for GC-MS analysis, complete analysis time was approximately 30 min, making the method suitable for clinical emergency toxicology purposes.
Jimmie L Valentine - One of the best experts on this subject based on the ideXlab platform.
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GC-MS Identification of Sympathomimetic Amine Drugs in Urine: Rapid Methodology Applicable for Emergency Clinical Toxicology
2016Co-Authors: Jimmie L Valentine, Rosalyn MiddletonAbstract:A method was developed that permitted rapid identification in urine of the following sympathomimetic amines: amphetamine, benzphetamine, cathinone, desmethylsegiline, diethylpropion, ephedrine, fenfluramine, mazindol, methylenedioxyamphetamine, methylenedioxyethylamphetamine, ethylenedioxymethamphetamine, mescaline, methamphetamine, methcathinone, methylaminorex, methylphenidate, pemoline, Phendimetrazine, phenylepherine, phentermine, phenylpropanolamine, pseudoephedrine, and selegiline. In addition, two c~-phenylethylamine-like monoamine oxidase inhibitors, phenelizine and tranylcypromine, were studied. Those sympathomimetic amines containing a primary o secondary amine, a hydrazine, and/or hydroxyl (except mazindol) functional groups were derivatized effectively using an on-column derivatization technique that used a reagent consisting of 10
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gc ms identification of sympathomimetic amine drugs in urine rapid methodology applicable for emergency clinical toxicology
Journal of Analytical Toxicology, 2000Co-Authors: Jimmie L Valentine, Rosalyn MiddletonAbstract:A method was developed that permitted rapid identification in urine of the following sympathomimetic amines: amphetamine, benzphetamine, cathinone, desmethylsegiline, diethylpropion, ephedrine, fenfluramine, mazindol, methylenedioxyamphetamine, methylenedioxyethylamphetamine, methylenedioxymethamphetamine, mescaline, methamphetamine, methcathinone, methylaminorex, methylphenidate, pemoline, Phendimetrazine, phenylepherine, phentermine, phenylpropanolamine, and selegiline. In two c~-phenylethylamine-like monoamine oxidase inhibitors, phenelizine and tranylcypromine, were studied. Those sympathomimetic amines containing a primary or secondary amine, a hydrazine, and/or hydroxyl (except mazindol) functional groups were derivatized effectively using an on-column derivatization technique that used a reagent consisting of 10% fluoroanhydride in hexane, whereas the other sympathomimetic amines, including mazindol, were analyzed underivatized. Three different fluoroanhydrides, trifluoroacetic (TFAA), pentafluoropropionic (PFPA), and heptafluorobutyric (HFBA), and three different injection-port temperatures (160, 200, and 260~ were investigated. Both TFAA and PFPA gave sympathomimetic amine derivatives with essentially identical retention times, whereas HFBA gave longer retention times and better separation of individual compounds. The base fragmentation ion was noted to increase 50 ainu (CF~) for each derivatized sympathomimetic amine as the length of the carbon-fluorine chain increased. Fragmentation ion abundance was maximized at injection-port temperature of 260~ and this enhanced sensitivity coupled with the better chromatographic resolution of the individual sympathomimetic amines prompted the selection of HFBA as the derivatizing agent of choice. Assignments were made for the fragmentation ions produced by each derivatized drug. The developed method was adapted to analyze urine specimens that might be encountered in emergency toxicology testing. For identification of sympathomimetic
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gc ms identification of sympathomimetic amine drugs in urine rapid methodology applicable for emergency clinical toxicology
Journal of Analytical Toxicology, 2000Co-Authors: Jimmie L Valentine, Rosalyn MiddletonAbstract:A method was developed that permitted rapid identification in urine of the following sympathomimetic amines: amphetamine, benzphetamine, cathinone, desmethylsegiline, diethylpropion, ephedrine, fenfluramine, mazindol, methylenedioxyamphetamine, methylenedioxyethylamphetamine, methylenedioxymethamphetamine, mescaline, methamphetamine, methcathinone, methylaminorex, methylphenidate, pemoline, Phendimetrazine, phenylepherine, phentermine, phenylpropanolamine, pseudoephedrine, and selegiline. In addition, two alpha-phenylethylamine-like monoamine oxidase inhibitors, phenelizine and tranylcypromine, were studied. Those sympathomimetic amines containing a primary or secondary amine, a hydrazine, and/or hydroxyl (except mazindol) functional groups were derivatized effectively using an on-column derivatization technique that used a reagent consisting of 10% fluoroanhydride in hexane, whereas the other sympathomimetic amines, including mazindol, were analyzed underivatized. Three different fluoroanhydrides, trifluoroacetic (TFAA), pentafluoropropionic (PFPA), and heptafluorobutyric (HFBA), and three different injection-port temperatures (160, 200, and 260 degrees C) were investigated. Both TFAA and PFPA gave sympathomimetic amine derivatives with essentially identical retention times, whereas HFBA gave longer retention times and better separation of individual compounds. The base fragmentation ion was noted to increase 50 amu (CF2) for each derivatized sympathomimetic amine as the length of the carbon-fluorine chain increased. Fragmentation ion abundance was maximized at an injection-port temperature of 260 degrees C, and this enhanced sensitivity coupled with the better chromatographic resolution of the individual sympathomimetic amines prompted the selection of HFBA as the derivatizing agent of choice. Assignments were made for the fragmentation ions produced by each derivatized drug. The developed method was adapted to analyze urine specimens that might be encountered in emergency toxicology testing. For identification of sympathomimetic amines requiring derivatization, 0.1 mL of the patient specimen had amphetamine-d5 and methamphetamine-d5 added as internal standard followed by adjustment of pH to 9.3 with borate buffer, extraction with 9:1 chloroform/isopropanol, centrifugation and separation of the organic phase, addition of 10% methanolic HCI and evaporation under nitrogen, reconstitution with HFBA reagent, and on-column derivatization during gas chromatographic-mass spectrometric (GC-MS) analysis. For those sympathomimetic amines not requiring derivatization, 1.0 mL of urine specimen had diazepam-d5 added as internal standard followed by the same extraction procedure and reconstitution accomplished with ethyl acetate. Because precolumn derivatization was eliminated and only 8 min was required for GC-MS analysis, complete analysis time was approximately 30 min, making the method suitable for clinical emergency toxicology purposes.