The Experts below are selected from a list of 495 Experts worldwide ranked by ideXlab platform
Martin D. Schechter - One of the best experts on this subject based on the ideXlab platform.
-
Differential training sequence effect upon psychostimulant discrimination
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 1993Co-Authors: Martin D. SchechterAbstract:Abstract Martin D. Schechter: Differential Training Sequence Effect Upon Psychostimulant Discrimination. Prog. Neuro-psychopharmacol. & Biol. Psychiat. 1993, 17 : (2) 319–327. 1. 1. Previous studies indicate that rats trained to discriminate either cathinone or Cathine from its vehicle have a diminished discriminative performance when tested 24 hours after a drug administration when compared to tests conducted after a vehicle administration. The phenomenon of rapid tolerance may occur to produce a lessened interoceptive cue on the test day following administration of the drug. It would, therefore, be probable that when rats are trained with consecutive cathinone or Cathine administrations they would perform less well than if they were trained with these drugs never given in consecutive training sessions. 2. 2. To test this hypothesis, rats were trained with 0.8 mg/kg l -cathinone or 4.8 mg/kg d -Cathine in a two-lever, food motivated operant task. Each of these groups were divided into two subgroups with the one receiving consecutive drug administrations and the second never receiving two consecutive administrations of the drug. 3. 3. Results indicate that in the Cathine-trained group, there was a significant increase in the time that was necessary to train the animals when consecutive administrations were used in training. This, however, did not occur in the cathinone-treated group. There was, however, no significant difference between the differentially trained groups as to ED50 values. 4. 4. It, thus, appears that there may not be a correlative relationship between speed of acquisition, as documented by sessions-to-criterion, and sensitivity, as indicated by ED50 values.
-
Lack of neuroleptic-like activity of l-fenfluramine.
Pharmacology Biochemistry and Behavior, 1991Co-Authors: Martin D. SchechterAbstract:Abstract Rats were trained to differentiate between the dopaminergically mediated discriminative stimuli produced by intraperitoneal administration of 4.8 mg/kg Cathine and its vehicle. Once trained, three doses of l -fenfluramine (1.0, 2.0 and 2.0 mg/kg) were administered to determine if this agent would produce Cathine-appropriate discriminative performance. All doses of l -fenfluramine were observed to produce vehicle-like responding. The 2.0 mg/kg dose of l -fenfluramine as well as 3.0 mg/kg chlorpromazine were administered in separate experiments prior to either Cathine or vehicle. Chlorpromazien attenuated Cathine-lever responding after Cathine administration but did not affect vehicle responding. In contrast, l -fenfluramine had no effect upon Cathine discrimination. The results indicate that l -fenfluramine shares neither agonist nor antagonist activity in the dopamine-mediated discriminative performance produced by Cathine.
-
discriminative stimulus properties of Cathine an alkaloid of the khat plant
Pharmacology Biochemistry and Behavior, 1990Co-Authors: Elizabeth A. Pehek, Martin D. SchechterAbstract:The effects of the psychostimulant (+)Cathine (norpseudoephedrine) were examined in a two-choice, food-motivated, drug-discrimination paradigm. Rats were able to discriminate Cathine from vehicle and this effect was dose- and time-dependent. Prior administration of Cathine resulted in a diminished response (tolerance) to subsequent Cathine and this effect developed and dissipated rapidly. Thus, different dose-response curves were generated depending upon whether Cathine or vehicle was administered the day before testing. The development of tolerance also shortened Cathine's time course of action and enhanced the ability of haloperidol to antagonize the Cathine cue. These results suggest caution in interpreting effects produced by intermittent drug injection schedules.
-
Rats become acutely tolerant to Cathine after amphetamine or cathinone administration
Psychopharmacology, 1990Co-Authors: Martin D. SchechterAbstract:The drug discrimination paradigm was used to evaluate in rats the ability of the discriminate response to either 0.8 mg/kg d -amphetamine or 0.8 mg/kg l -cathinone to generalize to 2.4–6.0 mg/kg of the active cathinone metabolite d -norpseudoephedrine, also known as Cathine. When tested 24 h after vehicle administration, Cathine generalized in a dose-related fashion in rats ( n =6) trained with cathinone (ED_50=3.03 mg/kg) and in rats ( n =8) trained with amphetamine (ED_50=2.93 mg/kg). In contrast, when Cathine was tested 24 h after the administration of either amphetamine or cathinone, it produced significantly decreased discriminative performance. The possibility that this acute tolerance may have been produced by release, and subsequent depletion, of brain dopamine was tested by pretreating rats with the dopamine release inhibitor CGS 10746B. When CGS 10746B was administered prior to cathinone it significantly decreased cathinone discrimination. In addition, acute tolerance to Cathine at 24 h after vehicle-cathinone co-administration was reversed when Cathine was tested 24 h after CGS 10746B-cathinone co-administration. The results suggest that cathinone-produced discriminative stimulus, as well as the acute tolerance to Cathine, may be dopaminergically mediated.
-
Dopaminergic nature of acute Cathine tolerance
Pharmacology Biochemistry and Behavior, 1990Co-Authors: Martin D. SchechterAbstract:Cathine is a psychoactive constituent in the leaves of the Khat shrub which are habitually ingested for their stimulatory effects in many parts of the world. Rats were trained to discriminate the stimulus effect of intraperitoneally administered 4.8 mg/kg d-Cathine and, once trained, administration of another Khat constituent, cathinone, was shown to produce Cathine-like effects. This generalization to cathinone was dose-responsive when testing occurred 24 hr after vehicle administration, whereas prior administration of Cathine resulted in a diminished discriminative response to subsequent cathinone administration possibly as a result of the development of acute tolerance. CGS 10746B, a compound that blocks presynaptic release of dopamine, significantly decreased rats' ability to discriminate Cathine when it was administered 25 min prior to Cathine testing and it reversed the acute tolerance observed when Cathine was tested 24 hr after Cathine administration. These results indicate that a previously reported acute tolerance effect to Cathine after cathinone administration in cathinone-trained rats appears to be symmetrical in that there is acute tolerance to cathinone after Cathine in these Cathine-trained rats. The results with CGS 10746B would suggest that both the Cathine-induced discriminative cue and Cathine's ability to produce acute tolerance are mediated by presynaptic dopamine release.
Barbara Morrissey - One of the best experts on this subject based on the ideXlab platform.
-
Detection and elimination profile of cathinone in equine after norephedrine (Propalin®) administration using a validated liquid chromatography–tandem mass spectrometry method
Analytical and Bioanalytical Chemistry, 2013Co-Authors: Sarah Zhao, Geoffrey Lam, Jasmeet Sandhu, Devan Loganathan, Barbara MorrisseyAbstract:Cathinone is the principal psychostimulant present in the leaves of khat shrub, which are widely used in East Africa and the Arab peninsula as an amphetamine-like stimulant. Cathinone readily undergoes metabolism in vivo to form less potent Cathine and norephedrine as the metabolites. However, the presence of Cathine and norephedrine in biological fluids cannot be used as an indicator of cathinone administration. The metabolism of pseudoephedrine and ephedrine, commonly used in cold and allergy medications, also produces Cathine and norephedrine, respectively, as the metabolites. Besides, Cathine and norephedrine may also originate from the ingestion of nutritional supplemental products containing extracts of Ephedra species. In Canada, ephedrine and norephedrine are available for veterinary use, whereas cathinone is not approved for human or veterinary use. In this article, the detection of cathinone in equine after administration of norephedrine is reported. To the best of our knowledge, this is the first such report in any species where administration of norephedrine or ephedrine generates cathinone as the metabolite. This observation is quite significant, because in equine detection of cathinone in biological fluids could be due to administration of the potent stimulant cathinone or the nonpotent stimulant norephedrine. A single oral dose of 450 mg norephedrine was administered to four Standardbred mares. Plasma and urine samples were collected up to 120 h after administration. The amount of cathinone and norephedrine detected in post administration samples was quantified using a highly sensitive, specific, and validated liquid chromatography–tandem mass spectrometry method. Using these results, we constructed elimination profiles for cathinone and norephedrine in equine plasma and urine. A mechanism that generates a geminal diol as an intermediate is postulated for this in vivo conversion of norephedrine to cathinone. Cathinone was also detected in samples collected after a single intramuscular administration of 200 mg ephedrine and oral administration of 300 mg ephedrine in equine. Figure Electron density structure of cathinone
-
Detection and elimination profile of cathinone in equine after norephedrine (Propalin®) administration using a validated liquid chromatography–tandem mass spectrometry method
Analytical and Bioanalytical Chemistry, 2013Co-Authors: Sarah Zhao, Geoffrey Lam, Jasmeet Sandhu, Devan Loganathan, Barbara MorrisseyAbstract:Cathinone is the principal psychostimulant present in the leaves of khat shrub, which are widely used in East Africa and the Arab peninsula as an amphetamine-like stimulant. Cathinone readily undergoes metabolism in vivo to form less potent Cathine and norephedrine as the metabolites. However, the presence of Cathine and norephedrine in biological fluids cannot be used as an indicator of cathinone administration. The metabolism of pseudoephedrine and ephedrine, commonly used in cold and allergy medications, also produces Cathine and norephedrine, respectively, as the metabolites. Besides, Cathine and norephedrine may also originate from the ingestion of nutritional supplemental products containing extracts of Ephedra species. In Canada, ephedrine and norephedrine are available for veterinary use, whereas cathinone is not approved for human or veterinary use. In this article, the detection of cathinone in equine after administration of norephedrine is reported. To the best of our knowledge, this is the first such report in any species where administration of norephedrine or ephedrine generates cathinone as the metabolite. This observation is quite significant, because in equine detection of cathinone in biological fluids could be due to administration of the potent stimulant cathinone or the nonpotent stimulant norephedrine. A single oral dose of 450 mg norephedrine was administered to four Standardbred mares. Plasma and urine samples were collected up to 120 h after administration. The amount of cathinone and norephedrine detected in post administration samples was quantified using a highly sensitive, specific, and validated liquid chromatography–tandem mass spectrometry method. Using these results, we constructed elimination profiles for cathinone and norephedrine in equine plasma and urine. A mechanism that generates a geminal diol as an intermediate is postulated for this in vivo conversion of norephedrine to cathinone. Cathinone was also detected in samples collected after a single intramuscular administration of 200 mg ephedrine and oral administration of 300 mg ephedrine in equine.
Bjørn Tore Gjertsen - One of the best experts on this subject based on the ideXlab platform.
-
RESEARCH ARTICLE Open Access
2016Co-Authors: Hans Jørgen Aarstad, Anne Christine Johannessen, Olav Karsten Vintermyr, Øystein Bruserud, Bjørn Tore GjertsenAbstract:Distinct single cell signal transduction signatures in leukocyte subsets stimulated with khat extract, amphetamine-like cathinone, Cathine or norephedrine Treatment with norephedrine resulted in significantly increased T-lymphocyte proliferation, whereas khat-extract Bredholt et al. BMC Pharmacology and Toxicology 2013, 14:3
-
Distinct single cell signal transduction signatures in leukocyte subsets stimulated with khat extract, amphetamine-like cathinone, Cathine or norephedrine
BMC Pharmacology and Toxicology, 2013Co-Authors: Therese Bredholt, Elisabeth Ersvær, Bjarte Skoe Erikstein, André Sulen, Håkon Reikvam, Hans Jørgen Aarstad, Anne Christine Johannessen, Olav Karsten Vintermyr, Øystein Bruserud, Bjørn Tore GjertsenAbstract:Background Amphetamine and amphetamine derivatives are suggested to induce an immunosuppressive effect. However, knowledge of how amphetamines modulate intracellular signaling pathways in cells of the immune system is limited. We have studied phosphorylation of signal transduction proteins (Akt, CREB, ERK1/2, NF-κB, c-Cbl, STAT1/3/5/6) and stress sensors (p38 MAPK, p53) in human leukocyte subsets following in vitro treatment with the natural amphetamine cathinone, the cathinone derivatives Cathine and norephedrine, in comparison with a defined extract of the psychostimulating herb khat ( Catha edulis Forsk.). Intracellular protein modifications in single cells were studied using immunostaining and flow cytometry, cell viability was determined by Annexin V-FITC/Propidium Iodide staining, and T-lymphocyte proliferation was measured by ^3H-thymidine incorporation. Results Cathinone, Cathine and norephedrine generally reduced post-translational modifications of intracellular signal transducers in T-lymphocytes, B-lymphocytes, natural killer cells and monocytes, most prominently affecting c-Cbl (pTyr700), ERK1/2 (p-Thr202/p-Tyr204), p38 MAPK (p-Thr180/p-Tyr182) and p53 (both total p53 protein and p-Ser15). In contrast, the botanical khat-extract induced protein phosphorylation of STAT1 (p-Tyr701), STAT6 (p-Tyr641), c-Cbl (pTyr700), ERK1/2 (p-Thr202/p-Tyr204), NF-κB (p-Ser529), Akt (p-Ser473), p38 MAPK (p-Thr180/p-Tyr182), p53 (Ser15) as well as total p53 protein. Cathinone, Cathine and norephedrine resulted in unique signaling profiles, with B-lymphocytes and natural killer cells more responsive compared to T-lymphocytes and monocytes. Treatment with norephedrine resulted in significantly increased T-lymphocyte proliferation, whereas khat-extract reduced proliferation and induced cell death. Conclusions Single-cell signal transduction analyses of leukocytes distinctively discriminated between stimulation with cathinone and the structurally similar derivatives Cathine and norephedrine. Cathinone, Cathine and norephedrine reduced phosphorylation of c-Cbl, ERK1/2, p38 MAPK and p53(Ser15), and norephedrine induced T-lymphocyte proliferation. Khat-extract induced protein phosphorylation of signal transducers, p38 MAPK and p53, followed by reduced cell proliferation and cell death. This study suggests that protein modification-specific single-cell analysis of immune cells could unravel pharmacologic effects of amphetamines and amphetamine-like agents, and further could represent a valuable tool in elucidation of mechanism(s) of action of complex botanical extracts.
-
Distinct single cell signal transduction signatures in leukocyte subsets stimulated with khat extract, amphetamine-like cathinone, Cathine or norephedrine
BMC Pharmacology and Toxicology, 2013Co-Authors: Therese Bredholt, Elisabeth Ersvær, Bjarte Skoe Erikstein, André Sulen, Håkon Reikvam, Hans Jørgen Aarstad, Anne Christine Johannessen, Olav Karsten Vintermyr, Øystein Bruserud, Bjørn Tore GjertsenAbstract:Background Amphetamine and amphetamine derivatives are suggested to induce an immunosuppressive effect. However, knowledge of how amphetamines modulate intracellular signaling pathways in cells of the immune system is limited. We have studied phosphorylation of signal transduction proteins (Akt, CREB, ERK1/2, NF-κB, c-Cbl, STAT1/3/5/6) and stress sensors (p38 MAPK, p53) in human leukocyte subsets following in vitro treatment with the natural amphetamine cathinone, the cathinone derivatives Cathine and norephedrine, in comparison with a defined extract of the psychostimulating herb khat (Catha edulis Forsk.). Intracellular protein modifications in single cells were studied using immunostaining and flow cytometry, cell viability was determined by Annexin V-FITC/Propidium Iodide staining, and T-lymphocyte proliferation was measured by 3H-thymidine incorporation.
Sarah Zhao - One of the best experts on this subject based on the ideXlab platform.
-
Detection and elimination profile of cathinone in equine after norephedrine (Propalin®) administration using a validated liquid chromatography–tandem mass spectrometry method
Analytical and Bioanalytical Chemistry, 2013Co-Authors: Sarah Zhao, Geoffrey Lam, Jasmeet Sandhu, Devan Loganathan, Barbara MorrisseyAbstract:Cathinone is the principal psychostimulant present in the leaves of khat shrub, which are widely used in East Africa and the Arab peninsula as an amphetamine-like stimulant. Cathinone readily undergoes metabolism in vivo to form less potent Cathine and norephedrine as the metabolites. However, the presence of Cathine and norephedrine in biological fluids cannot be used as an indicator of cathinone administration. The metabolism of pseudoephedrine and ephedrine, commonly used in cold and allergy medications, also produces Cathine and norephedrine, respectively, as the metabolites. Besides, Cathine and norephedrine may also originate from the ingestion of nutritional supplemental products containing extracts of Ephedra species. In Canada, ephedrine and norephedrine are available for veterinary use, whereas cathinone is not approved for human or veterinary use. In this article, the detection of cathinone in equine after administration of norephedrine is reported. To the best of our knowledge, this is the first such report in any species where administration of norephedrine or ephedrine generates cathinone as the metabolite. This observation is quite significant, because in equine detection of cathinone in biological fluids could be due to administration of the potent stimulant cathinone or the nonpotent stimulant norephedrine. A single oral dose of 450 mg norephedrine was administered to four Standardbred mares. Plasma and urine samples were collected up to 120 h after administration. The amount of cathinone and norephedrine detected in post administration samples was quantified using a highly sensitive, specific, and validated liquid chromatography–tandem mass spectrometry method. Using these results, we constructed elimination profiles for cathinone and norephedrine in equine plasma and urine. A mechanism that generates a geminal diol as an intermediate is postulated for this in vivo conversion of norephedrine to cathinone. Cathinone was also detected in samples collected after a single intramuscular administration of 200 mg ephedrine and oral administration of 300 mg ephedrine in equine. Figure Electron density structure of cathinone
-
Detection and elimination profile of cathinone in equine after norephedrine (Propalin®) administration using a validated liquid chromatography–tandem mass spectrometry method
Analytical and Bioanalytical Chemistry, 2013Co-Authors: Sarah Zhao, Geoffrey Lam, Jasmeet Sandhu, Devan Loganathan, Barbara MorrisseyAbstract:Cathinone is the principal psychostimulant present in the leaves of khat shrub, which are widely used in East Africa and the Arab peninsula as an amphetamine-like stimulant. Cathinone readily undergoes metabolism in vivo to form less potent Cathine and norephedrine as the metabolites. However, the presence of Cathine and norephedrine in biological fluids cannot be used as an indicator of cathinone administration. The metabolism of pseudoephedrine and ephedrine, commonly used in cold and allergy medications, also produces Cathine and norephedrine, respectively, as the metabolites. Besides, Cathine and norephedrine may also originate from the ingestion of nutritional supplemental products containing extracts of Ephedra species. In Canada, ephedrine and norephedrine are available for veterinary use, whereas cathinone is not approved for human or veterinary use. In this article, the detection of cathinone in equine after administration of norephedrine is reported. To the best of our knowledge, this is the first such report in any species where administration of norephedrine or ephedrine generates cathinone as the metabolite. This observation is quite significant, because in equine detection of cathinone in biological fluids could be due to administration of the potent stimulant cathinone or the nonpotent stimulant norephedrine. A single oral dose of 450 mg norephedrine was administered to four Standardbred mares. Plasma and urine samples were collected up to 120 h after administration. The amount of cathinone and norephedrine detected in post administration samples was quantified using a highly sensitive, specific, and validated liquid chromatography–tandem mass spectrometry method. Using these results, we constructed elimination profiles for cathinone and norephedrine in equine plasma and urine. A mechanism that generates a geminal diol as an intermediate is postulated for this in vivo conversion of norephedrine to cathinone. Cathinone was also detected in samples collected after a single intramuscular administration of 200 mg ephedrine and oral administration of 300 mg ephedrine in equine.
Devan Loganathan - One of the best experts on this subject based on the ideXlab platform.
-
Detection and elimination profile of cathinone in equine after norephedrine (Propalin®) administration using a validated liquid chromatography–tandem mass spectrometry method
Analytical and Bioanalytical Chemistry, 2013Co-Authors: Sarah Zhao, Geoffrey Lam, Jasmeet Sandhu, Devan Loganathan, Barbara MorrisseyAbstract:Cathinone is the principal psychostimulant present in the leaves of khat shrub, which are widely used in East Africa and the Arab peninsula as an amphetamine-like stimulant. Cathinone readily undergoes metabolism in vivo to form less potent Cathine and norephedrine as the metabolites. However, the presence of Cathine and norephedrine in biological fluids cannot be used as an indicator of cathinone administration. The metabolism of pseudoephedrine and ephedrine, commonly used in cold and allergy medications, also produces Cathine and norephedrine, respectively, as the metabolites. Besides, Cathine and norephedrine may also originate from the ingestion of nutritional supplemental products containing extracts of Ephedra species. In Canada, ephedrine and norephedrine are available for veterinary use, whereas cathinone is not approved for human or veterinary use. In this article, the detection of cathinone in equine after administration of norephedrine is reported. To the best of our knowledge, this is the first such report in any species where administration of norephedrine or ephedrine generates cathinone as the metabolite. This observation is quite significant, because in equine detection of cathinone in biological fluids could be due to administration of the potent stimulant cathinone or the nonpotent stimulant norephedrine. A single oral dose of 450 mg norephedrine was administered to four Standardbred mares. Plasma and urine samples were collected up to 120 h after administration. The amount of cathinone and norephedrine detected in post administration samples was quantified using a highly sensitive, specific, and validated liquid chromatography–tandem mass spectrometry method. Using these results, we constructed elimination profiles for cathinone and norephedrine in equine plasma and urine. A mechanism that generates a geminal diol as an intermediate is postulated for this in vivo conversion of norephedrine to cathinone. Cathinone was also detected in samples collected after a single intramuscular administration of 200 mg ephedrine and oral administration of 300 mg ephedrine in equine. Figure Electron density structure of cathinone
-
Detection and elimination profile of cathinone in equine after norephedrine (Propalin®) administration using a validated liquid chromatography–tandem mass spectrometry method
Analytical and Bioanalytical Chemistry, 2013Co-Authors: Sarah Zhao, Geoffrey Lam, Jasmeet Sandhu, Devan Loganathan, Barbara MorrisseyAbstract:Cathinone is the principal psychostimulant present in the leaves of khat shrub, which are widely used in East Africa and the Arab peninsula as an amphetamine-like stimulant. Cathinone readily undergoes metabolism in vivo to form less potent Cathine and norephedrine as the metabolites. However, the presence of Cathine and norephedrine in biological fluids cannot be used as an indicator of cathinone administration. The metabolism of pseudoephedrine and ephedrine, commonly used in cold and allergy medications, also produces Cathine and norephedrine, respectively, as the metabolites. Besides, Cathine and norephedrine may also originate from the ingestion of nutritional supplemental products containing extracts of Ephedra species. In Canada, ephedrine and norephedrine are available for veterinary use, whereas cathinone is not approved for human or veterinary use. In this article, the detection of cathinone in equine after administration of norephedrine is reported. To the best of our knowledge, this is the first such report in any species where administration of norephedrine or ephedrine generates cathinone as the metabolite. This observation is quite significant, because in equine detection of cathinone in biological fluids could be due to administration of the potent stimulant cathinone or the nonpotent stimulant norephedrine. A single oral dose of 450 mg norephedrine was administered to four Standardbred mares. Plasma and urine samples were collected up to 120 h after administration. The amount of cathinone and norephedrine detected in post administration samples was quantified using a highly sensitive, specific, and validated liquid chromatography–tandem mass spectrometry method. Using these results, we constructed elimination profiles for cathinone and norephedrine in equine plasma and urine. A mechanism that generates a geminal diol as an intermediate is postulated for this in vivo conversion of norephedrine to cathinone. Cathinone was also detected in samples collected after a single intramuscular administration of 200 mg ephedrine and oral administration of 300 mg ephedrine in equine.