The Experts below are selected from a list of 7209 Experts worldwide ranked by ideXlab platform
Tung M Fong - One of the best experts on this subject based on the ideXlab platform.
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effects of the cb1 cannabinoid receptor Inverse Agonist am251 on food intake and body weight in mice lacking μ opioid receptors
Brain Research, 2006Co-Authors: Richard Z Chen, Andrea Frassetto, Tung M FongAbstract:Abstract We used μ-opioid receptor-deficient (MOR−/−) mice to determine the effects of the CB1 cannabinoid receptor Inverse Agonist AM251 on feeding in the absence of MOR signaling. A single dose of AM251 at 0.6, 2 or 6 mg/kg caused similar dose-dependent suppression of food intake in wild-type and MOR−/− mice. Administration of AM251 at 3 mg/kg/day for 9 consecutive days also led to a similar reduction (∼8%) in body weight in wild-type and MOR−/− mice. Our results suggest that MOR signaling is not necessary for cannabinoid-mediated effects on feeding and that physiological antagonism of opioid receptor tone might be required for the observed synergistic effects of a CB1 Inverse Agonist and an opioid receptor antAgonist on feeding.
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effects of the cb1 cannabinoid receptor Inverse Agonist am251 on food intake and body weight in mice lacking μ opioid receptors
Brain Research, 2006Co-Authors: Richard Z Chen, Andrea Frassetto, Tung M FongAbstract:We used mu-opioid receptor-deficient (MOR-/-) mice to determine the effects of the CB1 cannabinoid receptor Inverse Agonist AM251 on feeding in the absence of MOR signaling. A single dose of AM251 at 0.6, 2 or 6 mg/kg caused similar dose-dependent suppression of food intake in wild-type and MOR-/- mice. Administration of AM251 at 3 mg/kg/day for 9 consecutive days also led to a similar reduction ( approximately 8%) in body weight in wild-type and MOR-/- mice. Our results suggest that MOR signaling is not necessary for cannabinoid-mediated effects on feeding and that physiological antagonism of opioid receptor tone might be required for the observed synergistic effects of a CB1 Inverse Agonist and an opioid receptor antAgonist on feeding.
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synergistic effects of cannabinoid Inverse Agonist am251 and opioid antAgonist nalmefene on food intake in mice
Brain Research, 2004Co-Authors: Richard Z Chen, Rueyruey C Huang, Chunpyn Shen, Douglas J Macneil, Tung M FongAbstract:Oral administration of the opioid antAgonist nalmefene alone (up to 20 mg/kg) failed to show a significant effect on acute food intake in mice. However, combined oral dosing of nalmefene and subthreshold doses of AM251, a cannabinoid CB1 receptor Inverse Agonist, led to a significant reduction in food intake in both lean and diet-induced obese (DIO) mice. Furthermore, the anorectic effect of a high dose of AM251 was further enhanced when co-administered with nalmefene. The results support a synergistic interaction between opioid and cannabinoid systems in regulating feeding behavior.
Ezio Tirelli - One of the best experts on this subject based on the ideXlab platform.
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the histamine h3 receptor Inverse Agonist pitolisant improves fear memory in mice
Behavioural Brain Research, 2013Co-Authors: Christian Brabant, Yana Charlier, Ezio TirelliAbstract:Abstract Numerous studies have demonstrated that brain histamine plays a crucial role in learning and memory and histamine H 3 receptor Inverse Agonists (H 3 R Inverse Agonists) have been proposed to treat cognitive disorders. Pitolisant (BF2.649, 1-{3-[3-(4-chlorophenyl)propoxy]propyl}piperidine, hydrochloride) was the first H 3 R Inverse Agonist that has been tested in human trials and is well tolerated. The present study investigated whether Pitolisant (0.625–20 mg/kg, i.p.) improves consolidation and reconsolidation processes in the fear conditioning task in female C57BL/6J mice. We also tested whether Pitolisant reverses memory deficits induced by the non-competitive N-methyl- d -aspartate (NMDA) antAgonist dizocilpine (MK-801). Our results indicate that post-training systemic injections of Pitolisant facilitated consolidation of contextual fear memory and reversed amnesia induced by an i.p. injection of 0.12 mg/kg dizocilpine. In addition, none of the doses of Pitolisant we have tested after reactivation (reexposure to the context in which training took place 48 h earlier) affected reconsolidation, whereas dizocilpine disrupted it. However, Pitolisant was able to reverse the deficit in reconsolidation induced by 0.12 mg/kg dizocilpine. The present results are the first demonstration that Pitolisant is effective in improving consolidation processes in the fear condition task and add further evidence to its potential for treating cognitive disorders.
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effects of the h 3 receptor Inverse Agonist thioperamide on cocaine induced locomotion in mice role of the histaminergic system and potential pharmacokinetic interactions
Psychopharmacology, 2009Co-Authors: Christian Brabant, Livia Alleva, Thierry Grisar, Etienne Quertemont, Bernard Lakaye, Hiroshi Ohtsu, Peter Jatlow, Marina R. Picciotto, Ezio TirelliAbstract:Rationale Previous studies have shown that intraperitoneal injections of thioperamide, an imidazole-based H3 receptor Inverse Agonist that enhances histamine release in the brain, potentiate cocaine-induced hyperlocomotion. The present study examined the involvement of the histaminergic system in these effects of thioperamide in mice.
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Effects of the H3 receptor Inverse Agonist thioperamide on cocaine-induced locomotion in mice: role of the histaminergic system and potential pharmacokinetic interactions
Psychopharmacology, 2008Co-Authors: Christian Brabant, Livia Alleva, Thierry Grisar, Etienne Quertemont, Bernard Lakaye, Hiroshi Ohtsu, Jian-sheng Lin, Peter Jatlow, Marina R. Picciotto, Ezio TirelliAbstract:Rationale Previous studies have shown that intraperitoneal injections of thioperamide, an imidazole-based H3 receptor Inverse Agonist that enhances histamine release in the brain, potentiate cocaine-induced hyperlocomotion. The present study examined the involvement of the histaminergic system in these effects of thioperamide in mice.
Lili Wang - One of the best experts on this subject based on the ideXlab platform.
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cannabinoid cb1 receptor Inverse Agonist mj08 stimulates glucose production via hepatic sympathetic innervation in rats
European Journal of Pharmacology, 2017Co-Authors: Hua Guan, Lili WangAbstract:Abstract As a key insulin target tissue for maintaining systemic glucose homeostasis, the liver plays important roles in improving obesity-associated insulin intolerance via selective cannabinoid CB1 receptor antagonism/Inverse agonism. However, it is unclear whether this receptor Inverse agonism affects hepatic glucose metabolism. MJ08 is a novel cannabinoid CB1 receptor antAgonist/Inverse Agonist that has superior Inverse agonism over the well-known antAgonist/Inverse Agonist, SR141716 (rimonabant). MJ08 remarkably elevates fasting blood glucose independent of inhibition of insulin release in mice. In the current study, MJ08 was used to investigate the mechanism by which liver cannabinoid CB1 receptor Inverse activation regulates hepatic glucose metabolism. MJ08 stimulated hepatic glucose production (HGP) in a dose-dependent manner and promoted gluconeogenic gene expression in perfused rat liver. SR141716 exhibited similar but weaker effects. The cannabinoid CB1 receptor Agonist (WIN 55,212-2), Gs protein-cyclic AMP (cAMP)-dependent pathway inhibitors (NF449 and H89), β-adrenoceptor antAgonist (propranolol), and peripheral sympathetic inhibitor (reserpine) could antagonize MJ08-induced HGP. Furthermore, MJ08 and SR141716 induced monoamine neurotransmitter (noradrenaline) release and increased cAMP content significantly in perfused liver, although only a slight increase was observed in primary cultured hepatocytes. These results indicate that local liver cannabinoid CB1 receptor Inverse agonism via hepatic sympathetic innervation is responsible for the HGP induced by MJ08. Thus, high Inverse Agonistic activity could increase fasting blood glucose levels and should be avoided in the development of peripheral cannabinoid CB1 receptor-targeted weight-loss drugs.
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cannabinoid cb 1 receptor Inverse Agonist mj08 stimulates glucose production via hepatic sympathetic innervation in rats
European Journal of Pharmacology, 2017Co-Authors: Wei Chen, Hua Guan, Hongying Liu, Nina Xue, Lili WangAbstract:As a key insulin target tissue for maintaining systemic glucose homeostasis, the liver plays important roles in improving obesity-associated insulin intolerance via selective cannabinoid CB1 receptor antagonism/Inverse agonism. However, it is unclear whether this receptor Inverse agonism affects hepatic glucose metabolism. MJ08 is a novel cannabinoid CB1 receptor antAgonist/Inverse Agonist that has superior Inverse agonism over the well-known antAgonist/Inverse Agonist, SR141716 (rimonabant). MJ08 remarkably elevates fasting blood glucose independent of inhibition of insulin release in mice. In the current study, MJ08 was used to investigate the mechanism by which liver cannabinoid CB1 receptor Inverse activation regulates hepatic glucose metabolism. MJ08 stimulated hepatic glucose production (HGP) in a dose-dependent manner and promoted gluconeogenic gene expression in perfused rat liver. SR141716 exhibited similar but weaker effects. The cannabinoid CB1 receptor Agonist (WIN 55,212-2), Gs protein-cyclic AMP (cAMP)-dependent pathway inhibitors (NF449 and H89), β-adrenoceptor antAgonist (propranolol), and peripheral sympathetic inhibitor (reserpine) could antagonize MJ08-induced HGP. Furthermore, MJ08 and SR141716 induced monoamine neurotransmitter (noradrenaline) release and increased cAMP content significantly in perfused liver, although only a slight increase was observed in primary cultured hepatocytes. These results indicate that local liver cannabinoid CB1 receptor Inverse agonism via hepatic sympathetic innervation is responsible for the HGP induced by MJ08. Thus, high Inverse Agonistic activity could increase fasting blood glucose levels and should be avoided in the development of peripheral cannabinoid CB1 receptor-targeted weight-loss drugs.
Takafumi Nagatomo - One of the best experts on this subject based on the ideXlab platform.
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assessment of binding affinity to 5 hydroxytryptamine 2a 5 ht2a receptor and Inverse Agonist activity of naftidrofuryl comparison with those of sarpogrelate
Journal of Pharmacological Sciences, 2009Co-Authors: Saida Abdel Regal Aly, Mohiuddin Ahmed Bhuiyan, Murad Hossain, Takashi Nakamura, Takafumi NagatomoAbstract:Naftidrofuryl is a peripheral vasodilator that has been clinically used in the treatment of intermittent claudication and dementia. It has 5-hydroxytryptamine 2 (5-HT2) antiserotonergic activity and selectively binds with the 5-HT2 receptor. The purpose of the present study is to assess the binding affinity and functional potency of naftidrofuryl to the 5-HT2A receptor, to find out the Inverse Agonist activity of this compound at a constitutively active mutant of 5-HT2A receptor, and finally to compare the findings with those of sarpogrelate. The investigation showed that the binding affinity (pKi) of naftidrofuryl was decreased 25- or 50-fold compared to sarpogrelate in the wild-type 5-HT2A receptor or Cys322Lys mutant receptor, respectively. Moreover, the functional potency (pKb) of naftidrofuryl was much lower compared to sarpogrelate at the 5-HT2A receptor. In addition, Inverse Agonist activity of naftidrofuryl was lower compared with sarpogrelate at the constitutively active mutant receptor. Thus, the data of the present study would be very important for the clarification of interaction sites of naftidrofuryl to 5-HT2A receptors and also may help to understand the mechanism of Inverse Agonist activity at the constitutively active mutant receptor.
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Inverse Agonist Activity of Sarpogrelate, a Selective 5-HT2A-Receptor AntAgonist, at the Constitutively Active Human 5-HT2A Receptor
Journal of Pharmacological Sciences, 2006Co-Authors: Habib Abul Muntasir, Mohiuddin Ahmed Bhuiyan, Masaji Ishiguro, Masanobu Ozaki, Takafumi NagatomoAbstract:Abstract Mutations producing constitutively active G-protein coupled receptors have been found in the pathophysiology of several diseases, implying that Inverse Agonists at the constitutively active receptors may have preferred therapeutic applications. Because of the involvement of 5-HT2A receptors in mediating many cardiovascular diseases, constitutively active mutants of the 5-HT2A receptor may be responsible for the disease states. Thus, the purpose of the present study was to investigate the Inverse Agonist activity of sarpogrelate, a selective 5-HT2A-receptor antAgonist, and its active metabolite, M-1; and we compared their activities with those of other 5-HT2A-receptor antAgonists such as ritanserin, ketanserin, and cyproheptadine. Using a constitutively active mutant (C322K) of the human 5-HT2A receptor, we demonstrated that like other 5-HT2A-receptor antAgonists, sarpogrelate acts as a potent Inverse Agonist by significantly reducing basal inositol phosphate levels. However, there were no significant differences between sarpogrelate and other 5-HT2A-receptor antAgonists for their Inverse Agonist activity. Compared with the wild type receptor, mutant receptor displayed significantly higher affinity for 5-HT and lower affinity for sarpogrelate. These results indicate that stabilization of the inactive conformation of the 5-HT2A receptor may be a key component of the mechanism of action of sarpogrelate.
Christian Brabant - One of the best experts on this subject based on the ideXlab platform.
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the histamine h3 receptor Inverse Agonist pitolisant improves fear memory in mice
Behavioural Brain Research, 2013Co-Authors: Christian Brabant, Yana Charlier, Ezio TirelliAbstract:Abstract Numerous studies have demonstrated that brain histamine plays a crucial role in learning and memory and histamine H 3 receptor Inverse Agonists (H 3 R Inverse Agonists) have been proposed to treat cognitive disorders. Pitolisant (BF2.649, 1-{3-[3-(4-chlorophenyl)propoxy]propyl}piperidine, hydrochloride) was the first H 3 R Inverse Agonist that has been tested in human trials and is well tolerated. The present study investigated whether Pitolisant (0.625–20 mg/kg, i.p.) improves consolidation and reconsolidation processes in the fear conditioning task in female C57BL/6J mice. We also tested whether Pitolisant reverses memory deficits induced by the non-competitive N-methyl- d -aspartate (NMDA) antAgonist dizocilpine (MK-801). Our results indicate that post-training systemic injections of Pitolisant facilitated consolidation of contextual fear memory and reversed amnesia induced by an i.p. injection of 0.12 mg/kg dizocilpine. In addition, none of the doses of Pitolisant we have tested after reactivation (reexposure to the context in which training took place 48 h earlier) affected reconsolidation, whereas dizocilpine disrupted it. However, Pitolisant was able to reverse the deficit in reconsolidation induced by 0.12 mg/kg dizocilpine. The present results are the first demonstration that Pitolisant is effective in improving consolidation processes in the fear condition task and add further evidence to its potential for treating cognitive disorders.
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effects of the h 3 receptor Inverse Agonist thioperamide on cocaine induced locomotion in mice role of the histaminergic system and potential pharmacokinetic interactions
Psychopharmacology, 2009Co-Authors: Christian Brabant, Livia Alleva, Thierry Grisar, Etienne Quertemont, Bernard Lakaye, Hiroshi Ohtsu, Peter Jatlow, Marina R. Picciotto, Ezio TirelliAbstract:Rationale Previous studies have shown that intraperitoneal injections of thioperamide, an imidazole-based H3 receptor Inverse Agonist that enhances histamine release in the brain, potentiate cocaine-induced hyperlocomotion. The present study examined the involvement of the histaminergic system in these effects of thioperamide in mice.
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Effects of the H3 receptor Inverse Agonist thioperamide on cocaine-induced locomotion in mice: role of the histaminergic system and potential pharmacokinetic interactions
Psychopharmacology, 2008Co-Authors: Christian Brabant, Livia Alleva, Thierry Grisar, Etienne Quertemont, Bernard Lakaye, Hiroshi Ohtsu, Jian-sheng Lin, Peter Jatlow, Marina R. Picciotto, Ezio TirelliAbstract:Rationale Previous studies have shown that intraperitoneal injections of thioperamide, an imidazole-based H3 receptor Inverse Agonist that enhances histamine release in the brain, potentiate cocaine-induced hyperlocomotion. The present study examined the involvement of the histaminergic system in these effects of thioperamide in mice.
