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David E. Spero - One of the best experts on this subject based on the ideXlab platform.
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Rimonabant (SR141716) has no effect on alcohol self-administration or endocrine measures in nontreatment-seeking heavy alcohol drinkers.
Psychopharmacology, 2009Co-Authors: David T. George, David Herion, Cheryl L. Jones, Monte J. Phillips, Jacqueline Hersh, Debra Hill, Markus Heilig, Vijay A. Ramchandani, Christopher B. Geyer, David E. SperoAbstract:Rationale There is an extensive literature showing that the CB1 Cannabinoid Receptor Antagonist rimonabant (SR141716) decreases alcohol consumption in animals, but little is known about its effects in human alcohol drinkers.
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Rimonabant (SR141716) has no effect on alcohol self-administration or endocrine measures in nontreatment-seeking heavy alcohol drinkers
Psychopharmacology, 2009Co-Authors: David T. George, David Herion, Cheryl L. Jones, Monte J. Phillips, Jacqueline Hersh, Debra Hill, Markus Heilig, Vijay A. Ramchandani, Christopher Geyer, David E. SperoAbstract:Rationale There is an extensive literature showing that the CB_1 Cannabinoid Receptor Antagonist rimonabant (SR141716) decreases alcohol consumption in animals, but little is known about its effects in human alcohol drinkers. Methods In this study, 49 nontreatment-seeking heavy alcohol drinkers participated in a 3-week study. After a 1-week baseline, participants received either 20 mg/day of rimonabant or placebo for 2 weeks under double-blind conditions. During these 3 weeks, participants reported their daily alcohol consumption by telephone. Subsequently, they participated in an alcohol self-administration paradigm in which they received a priming dose of alcohol followed by the option of consuming either eight alcohol drinks or receiving $3.00 for each nonconsumed drink. Endocrine measures and self-rating scales were also obtained. Results Rimonabant did not change alcohol consumption during the 2 weeks of daily call-ins. Similarly, the drug did not change either alcohol self-administration or endocrine measures during the laboratory session. Conclusion We conclude that the daily administration of 20 mg of rimonabant for 2 weeks has no effect on alcohol consumption in nontreatment-seeking heavy alcohol drinkers.
Philippe Soubrié - One of the best experts on this subject based on the ideXlab platform.
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SR 141716, a CB1 Cannabinoid Receptor Antagonist, selectively reduces sweet food intake in marmoset.
Behavioural pharmacology, 1998Co-Authors: Simiand J, M. Keane, P. E. Keane, Philippe SoubriéAbstract:SR 141716 (1 and 3 mg/kg p.o.), a selective central (CB1) Cannabinoid Receptor Antagonist, selectively reduced feeding of a very highly palatable cane-sugar mixture in marmosets. In contrast, standard primate pellet intake was not modified at the lower dose, but was slightly increased (+29%;p < 0.01) by the higher dose of SR 141716. These results are in agreement with the hypothesis that endogenous Cannabinoid systems are involved in the modulation of the appetitive value of food.
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selective inhibition of sucrose and ethanol intake by sr 141716 an Antagonist of central Cannabinoid cb1 Receptors
Psychopharmacology, 1997Co-Authors: Michele Arnone, Marie-hélène Thiébot, Jeanne Maruani, Frederique Chaperon, M Poncelet, Philippe SoubriéAbstract:SR 141716, a selective central CB1 Cannabinoid Receptor Antagonist, markedly and selectively reduces sucrose feeding and drinking as well as neuropeptide Y-induced sucrose drinking in rats. SR 141716 also decreases ethanol consumption in C57BL/6 mice. In contrast, blockade of CB1 Receptors only marginally affects regular chow intake or water drinking. The active doses of SR 141716 (0.3–3 mg/kg) are in the range known to antagonize the characteristic effects induced by Cannabinoid Receptor agonists. These results suggest for the first time that endogenous Cannabinoid systems may modulate the appetitive value of sucrose and ethanol, perhaps by affecting the activity of brain reward systems.
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Arousal-enhancing properties of the CB1 Cannabinoid Receptor Antagonist SR 141716A in rats as assessed by electroencephalographic spectral and sleep-waking cycle analysis
Life Sciences, 1996Co-Authors: Vincent Santucci, Jean Jacques Storme, Philippe Soubrié, Gérard Le FurAbstract:Abstract The effects of the central (CB1) Cannabinoid Receptor Antagonist SR 141716A on the sleep-waking cycle were investigated in freely-moving rats using time scoring and power spectral analysis of the electroencephalogram (EEG). Over a 4-hour recording period, SR 141716A (0.1, 0.3, 1, 3 and 10 mg/kg I.P.) dose-dependently increased the time spent in wakefulness at the expense of slow-wave sleep (SWS) and rapid eye movement sleep (REMS), delayed the occurrence of REMS but did not change the mean duration of REMS episodes. Moreover, the compound induced no change in motor behavior. At the efficient dose of 3 mg/kg I.P., SR 141716A reduced the spectral power of the EEG signals typical of SWS but did not affect those of wakefulness. Taken together, these results demonstrate that the EEG effects of SR 141716A reflect arousal-enhancing properties. In addition, the present study suggests that an endogenous Cannabinoid-like system is involved in the control of the sleep-waking cycle.
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Improvement of memory in rodents by the selective CB1 Cannabinoid Receptor Antagonist, SR 141716
Psychopharmacology, 1996Co-Authors: J. P. Terranova, J. J. Storme, N. Lafon, A. Pério, Murielle Rinaldi-carmona, G. Le Fur, Philippe SoubriéAbstract:Social short-term memory in rodents is based on the recognition of a juvenile by an adult conspecific when the juvenile is presented on two successive occasions. Cannabimimetics are claimed to induce memory deficits in both humans and animals. In the brain, they mainly bind to CB1 Receptors for which anandamide is a purported endogenous ligand. SR 141716, a specific Antagonist of CB1 Receptors, dose-dependently reverses biochemical and pharmacological effects of cannabimimetics. More particularly, it antagonizes the inhibition of hippocampal long-term potentiation induced by WIN 55,212-2 and anandamide, and it increases arousal when given alone. The present experiments study the ability of SR 141716 (from 0.03 to 3 mg/kg SC) to facilitate short-term olfactory memory in the social recognition test in rodents. SR 141716 improved social recognition in a long intertrial paradigm with a threshold dose of 0.1 mg/kg SC. At 1 mg/kg, it antagonized the memory disturbance elicited by retroactive inhibition. Scopolamine (0.06 mg/kg IP) partially reversed its memory-enhancing effect. Moreover, SR 141716 reduced memory deficit in aged rats (0.03–0.1 mg/kg) and mice (0.3–1 mg/kg). As SR 141716 is not known to exhibit any pharmacological activity which is not mediated by CB1 Receptors, the results strongly support the concept that blockade of CB1 Receptors plays an important role in consolidation of short-term memory in rodents and suggest there may be a role for an endogenous Cannabinoid agonist tone (anandaminergic) in forgetting.
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Biochemical and pharmacological characterisation of SR141716A, the first potent and selective brain Cannabinoid Receptor Antagonist.
Life sciences, 1995Co-Authors: Murielle Rinaldi-carmona, Philippe Soubrié, Francis Barth, Michel Heaulme, Richard Alonso, David Shire, Christian Congy, Jean-claude Breliere, Gérard Le FurAbstract:Abstract SR141716A is a selective, potent and orally active Antagonist of the brain Cannabinoid Receptor with a long duration of action. This compound shows high affinity for the central Cannabinoid Receptor (Ki=2 nM), displays low affinity for the peripheral Cannabinoid Receptor (Ki >1000 nM). In vitro , SR141716A antagonizes the inhibitory effects of Cannabinoid Receptor agonists on both mouse vas deferens contractions and dopamine-stimulated adenylyl cyclase activities in rat brain membranes. After oral administration SR141716A totally inhibited the ex vivo [3H]-CP55,940 binding to cerebral membranes with a ED50 value of 3.5 mg/kg. Furthermore SR141716A antagonizes the classical pharmacological responses elicited by Cannabinoid Receptor agonists. In addition, SR141716A reverses the inhibitory effect of WIN55212-2 on isoniazid-induced elevation of cGMP in rat cerebellum. This compound will provide a powerful tool for studying the in vivo functions of the anandamide/Cannabinoid system.
David T. George - One of the best experts on this subject based on the ideXlab platform.
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Rimonabant (SR141716) has no effect on alcohol self-administration or endocrine measures in nontreatment-seeking heavy alcohol drinkers.
Psychopharmacology, 2009Co-Authors: David T. George, David Herion, Cheryl L. Jones, Monte J. Phillips, Jacqueline Hersh, Debra Hill, Markus Heilig, Vijay A. Ramchandani, Christopher B. Geyer, David E. SperoAbstract:Rationale There is an extensive literature showing that the CB1 Cannabinoid Receptor Antagonist rimonabant (SR141716) decreases alcohol consumption in animals, but little is known about its effects in human alcohol drinkers.
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Rimonabant (SR141716) has no effect on alcohol self-administration or endocrine measures in nontreatment-seeking heavy alcohol drinkers
Psychopharmacology, 2009Co-Authors: David T. George, David Herion, Cheryl L. Jones, Monte J. Phillips, Jacqueline Hersh, Debra Hill, Markus Heilig, Vijay A. Ramchandani, Christopher Geyer, David E. SperoAbstract:Rationale There is an extensive literature showing that the CB_1 Cannabinoid Receptor Antagonist rimonabant (SR141716) decreases alcohol consumption in animals, but little is known about its effects in human alcohol drinkers. Methods In this study, 49 nontreatment-seeking heavy alcohol drinkers participated in a 3-week study. After a 1-week baseline, participants received either 20 mg/day of rimonabant or placebo for 2 weeks under double-blind conditions. During these 3 weeks, participants reported their daily alcohol consumption by telephone. Subsequently, they participated in an alcohol self-administration paradigm in which they received a priming dose of alcohol followed by the option of consuming either eight alcohol drinks or receiving $3.00 for each nonconsumed drink. Endocrine measures and self-rating scales were also obtained. Results Rimonabant did not change alcohol consumption during the 2 weeks of daily call-ins. Similarly, the drug did not change either alcohol self-administration or endocrine measures during the laboratory session. Conclusion We conclude that the daily administration of 20 mg of rimonabant for 2 weeks has no effect on alcohol consumption in nontreatment-seeking heavy alcohol drinkers.
Alexandros Makriyannis - One of the best experts on this subject based on the ideXlab platform.
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Effects of Cannabinoid Receptor Antagonists on maintenance and reinstatement of methamphetamine self-administration in rhesus monkeys.
European journal of pharmacology, 2010Co-Authors: Charles W Schindler, Alexandros Makriyannis, Leigh V Panlilio, Joanne P Gilman, Zuzana Justinova, V Kiran Vemuri, Steven R GoldbergAbstract:Cannabinoid Receptor Antagonists have shown some promise as treatments capable of reducing abuse and relapse to a number of abused drugs. In rodents, such effects have been observed with methamphetamine self-administration. However, the effects of Cannabinoid Receptor Antagonists on methamphetamine self-administration and relapse have not been studied in primates. In the present study, rhesus monkeys were trained to respond on a three-component operant schedule. During the first 5-min component, fixed-ratio responses were reinforced by food, during the second 90- or 180-min component fixed-ratio responses were reinforced by i.v. methamphetamine. The third component was identical to the first. There was a 5-min timeout between each component. The effects of the Cannabinoid Receptor Antagonists AM 251 and rimonabant were tested at various doses against self-administration of 3microg/kg/injection methamphetamine, and 1mg/kg AM 251 and 0.3mg/kg rimonabant were tested against the methamphetamine dose-effect function. The 1mg/kg dose of AM 251 was also tested for its ability to alter reinstatement of extinguished self-administration responding. The Cannabinoid Receptor Antagonist AM 251 was found to reduce methamphetamine self-administration at doses that did not affect food-reinforced responding. The Cannabinoid Receptor Antagonist rimonabant had similar, but less robust effects. AM 251 also prevented reinstatement of extinguished methamphetamine seeking that was induced by re-exposure to a combination of methamphetamine and methamphetamine-associated cues. These results indicate that Cannabinoid Receptor Antagonists might have therapeutic effects for the treatment of methamphetamine dependence.
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Effect of the Cannabinoid Receptor SPECT agent, AM 281, on hippocampal acetylcholine release from rat brain slices
Neuroscience Letters, 1997Co-Authors: Andrew N. Gifford, Ruoxi Lan, S. John Gatley, Yunjia Tang, Nora D. Volkow, Alexandros MakriyannisAbstract:The SPECT ligand AM 281, a less lipophilic analog of the Cannabinoid Receptor Antagonist SR 141716A, robustly potentiated electrically-evoked release of acetylcholine from superfused hippocampal slices and prevented the inhibition of acetylcholine release by the cannabimimetic drug WIN 55212-2. These results, similar to earlier observations with SR 141716A, indicate that AM 281 is either a Cannabinoid Receptor Antagonist or inverse agonist. Despite showing lower affinity than SR 141716A in hippocampal membrane binding experiments, AM 281 had slightly greater potency than SR 141716A in the hippocampal slice experiments, perhaps because of reduced drug absorption to slice membranes and to the apparatus.
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AM630 antagonism of Cannabinoid-stimulated [35S]GTPγS binding in the mouse brain
European Journal of Pharmacology, 1997Co-Authors: Yoshiaki Hosohata, Alexandros Makriyannis, Raymond M. Quock, Keiko Hosohata, Paul Consroe, William R. Roeske, Henry I. YamamuraAbstract:This research was designed to determine the action of the novel aminoalkylindole AM630 (6-iodo-pravadoline) at the Cannabinoid Receptor by studying its interaction with the Cannabinoid Receptor agonist WIN 55,212-2 (R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo [1,2,3-de]-1,4-benzoxazin-y]-(1-naphthalenyl)methanone mesylate) on guanosine-5'-O-(3-[35S]thio) triphosphate ([35S]GTP gamma S) binding in mouse brain. WIN 55,212-2 stimulated [35S]GTP gamma S binding, while AM630 had no effect. AM630 antagonized WIN 55,212-2-2induced [35S]GTP gamma S binding and shifted the WIN 55,212-dose-response curve to the right. These results clearly demonstrate that AM630 exerts Cannabinoid Receptor Antagonist properties in the brain.
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AM630 is a competitive Cannabinoid Receptor Antagonist in the guinea pig brain.
Life sciences, 1997Co-Authors: Keiko Hosohata, Alexandros Makriyannis, Yoshiaki Hosohata, Raymond M. Quock, Paul Consroe, William R. Roeske, T H Burkey, Henry I. YamamuraAbstract:AM630 has been demonstrated to be a Cannabinoid Receptor Antagonist in the mouse brain and vas deferens. Conversely, it was recently reported that AM630 acts as a Cannabinoid agonist in the guinea pig ileum. This research was designed to determine whether the difference in the action of AM630 is species specific. Studies conducted in guinea pig brain reveal that AM630 antagonizes the stimulatory effect of the Cannabinoid agonist WIN 55,212-2 on [35S]GTPgammaS binding suggesting that difference in AM630 activity in different tissues is not due to species variation.
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Preparation of iodine‐123 labeled AM251: A potential SPECT radioligand for the brain Cannabinoid CB1 Receptor
Journal of Labelled Compounds and Radiopharmaceuticals, 1996Co-Authors: Ruoxi Lan, S. John Gatley, Alexandros MakriyannisAbstract:We report the synthesis and labeling with iodine-123 of N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251). This compound is an analog of the recently described Cannabinoid Receptor Antagonist, SR141716A, in which a 4-chlorophenyl group is replaced by 4-iodophenyl. Labeling in good yield (62%) and radiochemical purity (< 95%), and high specific activity (< 2500 Ci/mmol) was achieved by an iododestannylation reaction using the tributyltin precursor, no carrier added I-123 iodide, and chloramine-T.
Markus Heilig - One of the best experts on this subject based on the ideXlab platform.
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A Cannabinoid Receptor Antagonist attenuates ghrelin-induced activation of the mesolimbic dopamine system in mice.
Physiology & behavior, 2017Co-Authors: Aimilia Lydia Kalafateli, Markus Heilig, Daniel Vallöf, Julia Winsa Jörnulf, Elisabet JerlhagAbstract:Ghrelin has been attributed various physiological processes including food intake and reward regulation, through activation of the mesolimbic dopamine system. Reward modulation involves the mesolimbic dopamine system, consisting of the ventral tegmental area (VTA) dopamine neurons targeting nucleus accumbens (NAc), a system that ghrelin activates through VTA-dependent mechanisms. In the first study, we found that systemic intraperitoneal (ip) administration of rimonabant attenuated intracerebroventricular (icv) ghrelin's ability to cause locomotor stimulation and NAc dopamine release in mice. Ghrelin-induced (icv) chow intake was not altered by rimonabant administration (ip). Finally, we showed that bilateral VTA administration of rimonabant blocks the ability of intra-VTA administered ghrelin to increase locomotor activity, but does not affect food intake in mice. Collectively, these data indicate clear dissociation between regulation of food intake and activation of the mesolimbic dopamine system.
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Rimonabant (SR141716) has no effect on alcohol self-administration or endocrine measures in nontreatment-seeking heavy alcohol drinkers.
Psychopharmacology, 2009Co-Authors: David T. George, David Herion, Cheryl L. Jones, Monte J. Phillips, Jacqueline Hersh, Debra Hill, Markus Heilig, Vijay A. Ramchandani, Christopher B. Geyer, David E. SperoAbstract:Rationale There is an extensive literature showing that the CB1 Cannabinoid Receptor Antagonist rimonabant (SR141716) decreases alcohol consumption in animals, but little is known about its effects in human alcohol drinkers.
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Rimonabant (SR141716) has no effect on alcohol self-administration or endocrine measures in nontreatment-seeking heavy alcohol drinkers
Psychopharmacology, 2009Co-Authors: David T. George, David Herion, Cheryl L. Jones, Monte J. Phillips, Jacqueline Hersh, Debra Hill, Markus Heilig, Vijay A. Ramchandani, Christopher Geyer, David E. SperoAbstract:Rationale There is an extensive literature showing that the CB_1 Cannabinoid Receptor Antagonist rimonabant (SR141716) decreases alcohol consumption in animals, but little is known about its effects in human alcohol drinkers. Methods In this study, 49 nontreatment-seeking heavy alcohol drinkers participated in a 3-week study. After a 1-week baseline, participants received either 20 mg/day of rimonabant or placebo for 2 weeks under double-blind conditions. During these 3 weeks, participants reported their daily alcohol consumption by telephone. Subsequently, they participated in an alcohol self-administration paradigm in which they received a priming dose of alcohol followed by the option of consuming either eight alcohol drinks or receiving $3.00 for each nonconsumed drink. Endocrine measures and self-rating scales were also obtained. Results Rimonabant did not change alcohol consumption during the 2 weeks of daily call-ins. Similarly, the drug did not change either alcohol self-administration or endocrine measures during the laboratory session. Conclusion We conclude that the daily administration of 20 mg of rimonabant for 2 weeks has no effect on alcohol consumption in nontreatment-seeking heavy alcohol drinkers.
