The Experts below are selected from a list of 27 Experts worldwide ranked by ideXlab platform
Leonard L Howell - One of the best experts on this subject based on the ideXlab platform.
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Effects of acute treatments with the Serotonin 2A antAgonist M100907 alone or in combination with the Serotonin 2C Agonist WAY163909 on methamphetamine self-administration in rhesus monkeys
Drug and alcohol dependence, 2018Co-Authors: Melis Odabas-geldiay, Kenner C Rice, Hannah Shields, Laís F. Berro, Leonard L HowellAbstract:Abstract Background Serotonin 5-HT2A receptor antAgonists and 5-HT2C receptor Agonists have been proposed as important candidates for the development of pharmacotherapies for psychostimulant abuse, with evidence suggesting that those receptors may act together to control behavior. However, the role of 5-HT2A receptors on the reinforcing effects of psychostimulant drugs has not been fully elucidated. Methods In the present study, we investigated the effects of the selective 5HT2A receptor antAgonist M100907 alone or in combination with the selective 5HT2C Agonist WAY 163909 on intravenous methamphetamine self-administration in rhesus macaques (N = 3). Methamphetamine self-administration (0.01-0.03 mg/kg/inf) was evaluated under a fixed-ratio 20-schedule of reinforcement, and acute pretreatments were conducted 1 h (M100907) or 45 min (WAY 163,909) prior to the beginning of self-administration sessions at the EDMax dose of methamphetamine once stability criteria were met. Results Pretreatment with M100907 (0.03–0.3 mg/kg, i.m.) dose-dependently attenuated methamphetamine self-administration, with the highest dose significantly decreasing response rates compared to vehicle. Combined administration of ineffective doses of M100907 and WAY 163,909 had no effects on methamphetamine self-administration. Conclusions Our study indicates that acute selective 5-HT2A receptor blockade decreases peak methamphetamine intake in nonhuman primates. Combination approaches with sub-threshold doses of 5-HT2A receptor antAgonists and 5-HT2C receptor Agonists, on the other hand, do not seem to be effective in decreasing methamphetamine reinforcement. Further studies are needed in order to investigate the effects of chronic treatments with M100 on complete METH SA dose-response curves.
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Effects of a Serotonin 2C Agonist and a 2A AntAgonist on Actigraphy-Based Sleep Parameters Disrupted by Methamphetamine Self-Administration in Rhesus Monkeys
Neuropsychopharmacology, 2017Co-Authors: Maylen Perez Diaz, Monica L Andersen, Kenner C Rice, Leonard L HowellAbstract:Sleep disorders and substance abuse are highly comorbid and we have previously shown that methamphetamine self-administration significantly disrupts activity-based sleep parameters in rhesus monkeys. To the best of our knowledge, no study has evaluated the effectiveness of any pharmacological intervention to attenuate the effects of methamphetamine on nighttime activity under well-controlled conditions in laboratory animals. Thus, we examined the effects of a 5-HT_2C receptor Agonist, WAY163909, and a 5-HT_2A receptor antAgonist, M100907, given alone and in combination, on actigraphy-based sleep parameters disrupted by methamphetamine self-administration in non-human primates. Adult male/female rhesus monkeys self-administered methamphetamine (0.03 mg/kg/injection, i.v.) under a fixed-ratio 20 schedule of reinforcement (60-min sessions once a day, 5 days per week). Nighttime activity was evaluated using Actiwatch monitors. WAY163909 (0.1, 0.3, and 1.0 mg/kg), M100907 (0.03, 0.1, and 0.3 mg/kg), and a combination (0.1 mg/kg M100+0.3 mg/kg WAY) were administered i.m. before lights-out. Each dose was given for five consecutive days during which self-administration took place in the morning. Both drugs improved activity-based sleep measures disrupted by methamphetamine by decreasing sleep latency and increasing sleep efficiency compared with vehicle. By combining these drugs, their individual effects were significantly enhanced. Agonists at the 5-HT_2C receptor and antAgonists at the 5-HT_2A receptor show promise as potential treatments for the sleep-disrupting effects of stimulants when used alone and in combination. Combining subthreshold doses of WAY and M100 produced significant improvements in nighttime activity measures while avoiding the general motor-decreasing effects of the high dose of WAY.
Alan P. Kozikowski - One of the best experts on this subject based on the ideXlab platform.
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Design and Synthesis of (2-(5-Chloro-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)cyclopropyl)methanamine as a Selective Serotonin 2C Agonist.
Tetrahedron letters, 2015Co-Authors: Jianjun Cheng, Patrick M. Giguère, Bryan L. Roth, Alan P. KozikowskiAbstract:A conformationally restricted analog of a selective cyclopropane-bearing Serotonin 2C Agonist was designed and synthesized. A 2,2-dimethyl-2,3-dihydrobenzofuran scaffold was investigated as a constrained variant of a biologically active isopropyl phenyl ether. Construction of the required dimethyl-2,3-dihydrobenzofuran intermediate began using a procedure that relied on a microwave-assisted alkylation reaction. The synthesis of the designed compound as its HCl salt is reported in a total of 12 steps and 17% overall yield. Biological evaluation revealed the constrained analog to be a selective Serotonin 2C Agonist with modest potency.
Kenner C Rice - One of the best experts on this subject based on the ideXlab platform.
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Effects of acute treatments with the Serotonin 2A antAgonist M100907 alone or in combination with the Serotonin 2C Agonist WAY163909 on methamphetamine self-administration in rhesus monkeys
Drug and alcohol dependence, 2018Co-Authors: Melis Odabas-geldiay, Kenner C Rice, Hannah Shields, Laís F. Berro, Leonard L HowellAbstract:Abstract Background Serotonin 5-HT2A receptor antAgonists and 5-HT2C receptor Agonists have been proposed as important candidates for the development of pharmacotherapies for psychostimulant abuse, with evidence suggesting that those receptors may act together to control behavior. However, the role of 5-HT2A receptors on the reinforcing effects of psychostimulant drugs has not been fully elucidated. Methods In the present study, we investigated the effects of the selective 5HT2A receptor antAgonist M100907 alone or in combination with the selective 5HT2C Agonist WAY 163909 on intravenous methamphetamine self-administration in rhesus macaques (N = 3). Methamphetamine self-administration (0.01-0.03 mg/kg/inf) was evaluated under a fixed-ratio 20-schedule of reinforcement, and acute pretreatments were conducted 1 h (M100907) or 45 min (WAY 163,909) prior to the beginning of self-administration sessions at the EDMax dose of methamphetamine once stability criteria were met. Results Pretreatment with M100907 (0.03–0.3 mg/kg, i.m.) dose-dependently attenuated methamphetamine self-administration, with the highest dose significantly decreasing response rates compared to vehicle. Combined administration of ineffective doses of M100907 and WAY 163,909 had no effects on methamphetamine self-administration. Conclusions Our study indicates that acute selective 5-HT2A receptor blockade decreases peak methamphetamine intake in nonhuman primates. Combination approaches with sub-threshold doses of 5-HT2A receptor antAgonists and 5-HT2C receptor Agonists, on the other hand, do not seem to be effective in decreasing methamphetamine reinforcement. Further studies are needed in order to investigate the effects of chronic treatments with M100 on complete METH SA dose-response curves.
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Effects of a Serotonin 2C Agonist and a 2A AntAgonist on Actigraphy-Based Sleep Parameters Disrupted by Methamphetamine Self-Administration in Rhesus Monkeys
Neuropsychopharmacology, 2017Co-Authors: Maylen Perez Diaz, Monica L Andersen, Kenner C Rice, Leonard L HowellAbstract:Sleep disorders and substance abuse are highly comorbid and we have previously shown that methamphetamine self-administration significantly disrupts activity-based sleep parameters in rhesus monkeys. To the best of our knowledge, no study has evaluated the effectiveness of any pharmacological intervention to attenuate the effects of methamphetamine on nighttime activity under well-controlled conditions in laboratory animals. Thus, we examined the effects of a 5-HT_2C receptor Agonist, WAY163909, and a 5-HT_2A receptor antAgonist, M100907, given alone and in combination, on actigraphy-based sleep parameters disrupted by methamphetamine self-administration in non-human primates. Adult male/female rhesus monkeys self-administered methamphetamine (0.03 mg/kg/injection, i.v.) under a fixed-ratio 20 schedule of reinforcement (60-min sessions once a day, 5 days per week). Nighttime activity was evaluated using Actiwatch monitors. WAY163909 (0.1, 0.3, and 1.0 mg/kg), M100907 (0.03, 0.1, and 0.3 mg/kg), and a combination (0.1 mg/kg M100+0.3 mg/kg WAY) were administered i.m. before lights-out. Each dose was given for five consecutive days during which self-administration took place in the morning. Both drugs improved activity-based sleep measures disrupted by methamphetamine by decreasing sleep latency and increasing sleep efficiency compared with vehicle. By combining these drugs, their individual effects were significantly enhanced. Agonists at the 5-HT_2C receptor and antAgonists at the 5-HT_2A receptor show promise as potential treatments for the sleep-disrupting effects of stimulants when used alone and in combination. Combining subthreshold doses of WAY and M100 produced significant improvements in nighttime activity measures while avoiding the general motor-decreasing effects of the high dose of WAY.
Jianjun Cheng - One of the best experts on this subject based on the ideXlab platform.
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Design and Synthesis of (2-(5-Chloro-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)cyclopropyl)methanamine as a Selective Serotonin 2C Agonist.
Tetrahedron letters, 2015Co-Authors: Jianjun Cheng, Patrick M. Giguère, Bryan L. Roth, Alan P. KozikowskiAbstract:A conformationally restricted analog of a selective cyclopropane-bearing Serotonin 2C Agonist was designed and synthesized. A 2,2-dimethyl-2,3-dihydrobenzofuran scaffold was investigated as a constrained variant of a biologically active isopropyl phenyl ether. Construction of the required dimethyl-2,3-dihydrobenzofuran intermediate began using a procedure that relied on a microwave-assisted alkylation reaction. The synthesis of the designed compound as its HCl salt is reported in a total of 12 steps and 17% overall yield. Biological evaluation revealed the constrained analog to be a selective Serotonin 2C Agonist with modest potency.
William L. Baker - One of the best experts on this subject based on the ideXlab platform.
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Lorcaserin: a novel Serotonin 2C Agonist for the treatment of obesity
Current medical research and opinion, 2013Co-Authors: Stefanie C. Nigro, Darren Luon, William L. BakerAbstract:AbstractBackground:Obesity has become an epidemic in the United States and its prevalence continues to increase. Adjunctive treatment with pharmacotherapy is often reserved for individuals who fail to achieve their intended weight goals with diet and exercise alone. Current approved therapies for weight loss include phentermine, diethylpropion, orlistat, and phentermine/topiramate. The objective of this paper was to review the place of lorcaserin, a novel Serotonin 2C Agonist, which was FDA approved in July 2012. Unlike contemporary lipase inhibitors and sympathomimetic amines, lorcaserin is purported to reduce food consumption and increase satiety.Scope:A systematic review of the literature for all relevant articles was performed through January 2013 using MEDLINE, Web of Science, and International Pharmaceutical Abstracts using key words related to lorcaserin.Findings:Three phase III clinical studies have been published evaluating the efficacy and safety of lorcaserin in various obese populations. A hig...
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Brief review Lorcaserin: a novel Serotonin 2C Agonist for the treatment of obesity
2013Co-Authors: Stefanie C. Nigro, Darren Luon, William L. BakerAbstract:Background: Obesity has become an epidemic in the United States and its prevalence continues to increase. Adjunctive treatment with pharmacotherapy is often reserved for individuals who fail to achieve their intended weight goals with diet and exercise alone. Current approved therapies for weight loss include phentermine, diethylpropion, orlistat, and phentermine/topiramate. The objective of this paper was to review the place of lorcaserin, a novel Serotonin 2C Agonist, which was FDA approved in July 2012. Unlike contemporary lipase inhibitors and sympathomimetic amines, lorcaserin is purported to reduce food consumption and increase satiety.
