piperidines and Anorexia

piperidines has been researched along with Anorexia* in 22 studies

Reviews

4 review(s) available for piperidines and Anorexia

ArticleYear
Role of the endocannabinoid system in metabolic control.
    Current opinion in nephrology and hypertension, 2008, Volume: 17, Issue:1

    Growing evidence suggests an important role in metabolic control of the endocannabinoid system, which is composed of cannabinoid receptors, endocannabinoids, and related enzymes. In this short review, we describe the latest advances in this research field, including the antiobesity effect of the cannabinoid receptor CB1 antagonist rimonabant and the anorexic effect of N-oleoylethanolamine, an endocannabinoid-related, endogenous substance.. CB1 is expressed not only in various brain regions, including hypothalamus, but also in peripheral organs such as adipose tissue and liver. The endocannabinoid system appears to function as a physiological system regulating food intake, energy balance, and lipid metabolism through both central and peripheral mechanisms. Obesity may be associated with hyperactivity of the endocannabinoid system. Large phase III trials of rimonabant confirmed significant weight loss and waist circumference reduction in overweight and obese patients. The levels of HDL-cholesterol, triglycerides, and HbA1c were also improved. The anorexic effect of N-oleoylethanolamine was suggested to be mediated by peroxisome proliferator-activated receptor-alpha and the G protein-coupled receptor GPR119.. These results highlight the importance of an endocannabinoid tone in metabolic control and therapeutic usefulness of CB1 antagonists. Derivatives of N-oleoylethanolamine may be developed as new antiobesity drugs.

    Topics: Anorexia; Cannabinoid Receptor Modulators; Central Nervous System; Endocannabinoids; Ethanolamines; Humans; Obesity; Oleic Acids; Piperidines; Pyrazoles; Rimonabant

2008
Central versus peripheral antagonism of cannabinoid CB1 receptor in obesity: effects of LH-21, a peripherally acting neutral cannabinoid receptor antagonist, in Zucker rats.
    Journal of neuroendocrinology, 2008, Volume: 20 Suppl 1

    The endogenous cannabinoid system plays an important modulatory role in feeding behaviour and metabolism, acting at both central and peripheral levels. Chronic administration of cannabinoid CB(1) receptor antagonists has been found to be effective in experimental obesity. However, clinically available cannabinoid receptor antagonists are inverse agonists that can target CB(1) receptors located in both central circuits regulating appetite and motivation and in peripheral organs regulating metabolism and energy expenditure. This profile complicates understanding of cannabinoid CB(1) receptor blockade as a therapeutic strategy in obesity and metabolic disorders. This review aims to explore the relevance of both inverse agonism and peripheral cannabinoid receptor blockade on the beneficial actions of chronic cannabinoid receptor blockade, by comparing the actions of the reference antagonist/inverse agonist rimonabant and the newly designed drug LH-21. LH-21 is a triazol derivative and a neutral cannabinoid receptor antagonist; it has a poor penetration rate into the central nervous system. When given acutely it decreases food intake and enhances the anorectic actions of oleoylethanolamide, a feeding suppressant lipid that acts on peripheral sensory terminals in a similar way as rimonabant. Unlike rimonabant, chronic administration of LH-21 (3 mg/kg) reduces feeding but does not improve hypertriglyceridaemia or hypercholesterolaemia; nor does it reduce liver fat deposits in Zucker rats. These results suggest that the inverse agonism and/or the antagonism of central cannabinoid CB(1) receptors are necessary for the metabolic benefits of cannabinoid CB(1) receptor blockade, but not for the appetite reduction.

    Topics: Animals; Anorexia; Anti-Obesity Agents; Biological Availability; Brain; Cannabinoids; Central Nervous System; Drug Synergism; Eating; Endocannabinoids; Energy Metabolism; Feeding Behavior; Obesity; Oleic Acids; Piperidines; Pyrazoles; Rats; Rats, Zucker; Receptor, Cannabinoid, CB1; Rimonabant; Triazoles

2008
Donepezil (Aricept) for treatment of Alzheimer's disease and other dementing conditions.
    Expert review of neurotherapeutics, 2004, Volume: 4, Issue:1

    Alzheimer's disease is common, incurable and disabling. It is expected to grow dramatically in prevalence over the next 50 years. At current, the standard of care for patients with mild and moderately severe Alzheimer's disease includes the use of acetylcholinesterase inhibitors. Donepezil (Aricept) is a highly selective acetylcholinesterase inhibitors with a pharmacokinetic profile allowing once-daily dosing. There is an extensive knowledge base derived from published clinical trials of donepezil in Alzheimer's disease, revealing consistent efficacy in cognition, global clinical ratings and daily function. Donepezil is also associated with additional meaningful outcomes such as reduced risk for, or delay to, nursing home placement. Despite a sense of limited efficacy of this drug class among prescribers, number needed-to-treat analyses suggest donepezil is highly effective at reducing the long-term adverse outcomes associated with Alzheimer's disease.

    Topics: Alzheimer Disease; Anorexia; Cholinesterase Inhibitors; Clinical Trials as Topic; Cognition Disorders; Dementia; Diarrhea; Donepezil; Drug Interactions; Humans; Indans; Nausea; Piperidines; Treatment Outcome; Vomiting

2004
Donepezil: an anticholinesterase inhibitor for Alzheimer's disease.
    American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 1997, Dec-15, Volume: 54, Issue:24

    The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of donepezil are reviewed. Donepezil is a synthetic noncovalent reversible inhibitor of acetylcholinesterase (AChE) for the treatment of mild to moderate dementia associated with Alzheimer's disease. In contrast to tacrine hydrochloride, the only comparable agent currently approved by FDA, donepezil exhibits a relatively high degree of selectivity for neuronal AChE as opposed to butyrylcholinesterase. It has a half-life of 60 hours in young adults and 104 hours in elderly patients. In clinical trials, donepezil has been associated with significant improvements in Alzheimer's Disease Assessment Scale-cognitive subscale and Clinical Interview-Based Impression of Change scores. The most common adverse effects associated with donepezil are nausea, diarrhea, anorexia, and vomiting, which are most likely to occur during dose initiation or adjustment. Hepatotoxicity, a dose-limiting adverse effect that sometimes requires discontinuation of tacrine, has not been reported with donepezil. Donepezil does not appear to interact with theophylline, cimetidine, warfarin, or digoxin. Ketoconazole and quinidine inhibit the metabolism of donepezil in vitro, but there is a lack of clinical data showing that these drugs decrease the clearance of donepezil. The initial recommended dosage is 5 mg daily before bedtime, with a dosage increase to 10 mg after four to six weeks according to the patient's response and tolerance. Donepezil appears to be preferable to tacrine as the initial agent for patients with mild to moderate dementia associated with Alzheimer's disease.

    Topics: Aged; Alzheimer Disease; Anorexia; Cholinesterase Inhibitors; Diarrhea; Donepezil; Drug Administration Schedule; Drug Interactions; Humans; Indans; Nausea; Piperidines

1997

Trials

1 trial(s) available for piperidines and Anorexia

ArticleYear
Phase II trial of flavopiridol, a cyclin dependent kinase inhibitor, in untreated metastatic malignant melanoma.
    Investigational new drugs, 2004, Volume: 22, Issue:3

    To test the activity of the cyclin dependent kinase (cdk) inhibitor flavopiridol in malignant melanoma, a disease with frequent abnormalities of the cyclin dependent kinase system.. Patients had histologically proven, unidimensionally measurable malignant melanoma, incurable by standard therapy. Prior adjuvant immunotherapy was allowed, but patients were otherwise untreated for advanced disease. Flavopiridol was administered at a dose of 50 mg/m(2) IV over 1 hour daily x 3 days every 3 weeks. Patients were assessed for response every 2 cycles.. 17 patients were accrued over 5 months. No objective responses were documented in the 16 patients evaluable for response. Seven patients (44%) had stable disease after 2 cycles, with a median of 2.8 months (range 1.8-9.2). The most common treatment-related non-hematologic toxicities were diarrhea (82%), nausea (47%), fatigue (41%), anorexia (35%) and vomiting (29%). Most treatment-related toxicities were mild, except for diarrhea (grade 3 in 3 patients, grade 4 in 1 patient), nausea (grade 3 in 1 patient) and tumor pain (grade 3 in 1 patient). Hematologic toxicities were minimal, none worse than grade 2. Eighty-eight percent of patients received >/=90% planned dose intensity; 2 patients had dose reductions for gastrointestinal (GI) toxicity.. Flavopiridol is well tolerated at the dose regimen used in this study, with an acceptable (primarily GI) toxicity profile. Although 7 of the 16 patients had stable disease ranging from 1.8 to 9.2 months in duration, there was no evidence of significant clinical activity in malignant melanoma by objective response criteria.

    Topics: Adult; Aged; Anorexia; Antineoplastic Agents; Cyclin-Dependent Kinases; Diarrhea; Fatigue; Female; Flavonoids; Humans; Infusions, Intravenous; Male; Maximum Tolerated Dose; Melanoma; Middle Aged; Neoplasm Metastasis; Piperidines; Treatment Outcome; Vomiting

2004

Other Studies

17 other study(ies) available for piperidines and Anorexia

ArticleYear
Abnormal response to the anorexic effect of GHS-R inhibitors and exenatide in male Snord116 deletion mouse model for Prader-Willi syndrome.
    Endocrinology, 2014, Volume: 155, Issue:7

    Prader-Willi syndrome (PWS) is a genetic disease characterized by persistent hunger and hyperphagia. The lack of the Snord116 small nucleolar RNA cluster has been identified as the major contributor to PWS symptoms. The Snord116 deletion (Snord116del) mouse model manifested a subset of PWS symptoms including hyperphagia and hyperghrelinemia. In this study, male Snord116del mice were characterized and tested for their acute and chronic responses to anorexic substances related to the ghrelin pathway. In comparison with their wild-type littermates, the food intake rate of Snord116del mice was 14% higher when fed ad libitum, and 32% to 49% higher within 12 hours after fasting. Fasted Snord116del mice were less sensitive to the acute anorexic effect of competitive antagonist [d-Lys(3)]-GHRP6, YIL-781, and reverse agonist [d-Arg(1),d-Phe(5),d-Trp(7,9),Leu(11)]-substance P (SPA) of ghrelin receptor GHS-R. All 3 GHS-R inhibitors failed to inhibit chronic food intake of either Snord116del or wild-type mice due to rapid adaptation. Although fasted Snord116del mice had normal sensitivity to the acute anorexic effect of glucagon-like peptide 1 receptor agonist exenatide, those fed ad libitum required a higher dose and more frequent delivery to achieve ∼15% suppression of long-term food intake in comparison with wild-type mice. Ghrelin, however, is unlikely to be essential for the anorexic effect of exenatide in fed mice, as shown by the fact that exenatide did not reduce ghrelin levels in fed mice and food intake of ghrelin(-/-) mice fed ad libitum could be suppressed by exenatide. In conclusion, this study suggests that GHS-R may not be an effective therapeutic target, and in contrast, exenatide may produce anorexic effect in PWS individuals.

    Topics: Analysis of Variance; Animals; Anorexia; Disease Models, Animal; Eating; Exenatide; Fasting; Ghrelin; Humans; Hyperphagia; Hypoglycemic Agents; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Oligopeptides; Peptides; Piperidines; Prader-Willi Syndrome; Quinazolinones; Receptors, Ghrelin; RNA, Small Nucleolar; Substance P; Venoms

2014
Rimonabant precipitates anxiety in rats withdrawn from palatable food: role of the central amygdala.
    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2013, Volume: 38, Issue:12

    The anti-obesity medication rimonabant, an antagonist of cannabinoid type-1 (CB(1)) receptor, was withdrawn from the market because of adverse psychiatric side effects, including a negative affective state. We investigated whether rimonabant precipitates a negative emotional state in rats withdrawn from palatable food cycling. The effects of systemic administration of rimonabant on anxiety-like behavior, food intake, body weight, and adrenocortical activation were assessed in female rats during withdrawal from chronic palatable diet cycling. The levels of the endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG), and the CB(1) receptor mRNA and the protein in the central nucleus of the amygdala (CeA) were also investigated. Finally, the effects of microinfusion of rimonabant in the CeA on anxiety-like behavior, and food intake were assessed. Systemic administration of rimonabant precipitated anxiety-like behavior and anorexia of the regular chow diet in rats withdrawn from palatable diet cycling, independently from the degree of adrenocortical activation. These behavioral observations were accompanied by increased 2-AG, CB(1) receptor mRNA, and protein levels selectively in the CeA. Finally, rimonabant, microinfused directly into the CeA, precipitated anxiety-like behavior and anorexia. Our data show that (i) the 2-AG-CB(1) receptor system within the CeA is recruited during abstinence from palatable diet cycling as a compensatory mechanism to dampen anxiety, and (ii) rimonabant precipitates a negative emotional state by blocking the beneficial heightened 2-AG-CB(1) receptor signaling in this brain area. These findings help elucidate the link between compulsive eating and anxiety, and it will be valuable to develop better pharmacological treatments for eating disorders and obesity.

    Topics: Amygdala; Animals; Anorexia; Anti-Obesity Agents; Anxiety; Arachidonic Acids; Body Weight; Cannabinoid Receptor Antagonists; Corticosterone; Diet; Dietary Sucrose; Endocannabinoids; Female; Glycerides; Piperidines; Pyrazoles; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Rimonabant

2013
NR2B subunit of the NMDA glutamate receptor regulates appetite in the parabrachial nucleus.
    Proceedings of the National Academy of Sciences of the United States of America, 2013, Sep-03, Volume: 110, Issue:36

    Diphtheria toxin-mediated, acute ablation of hypothalamic neurons expressing agouti-related protein (AgRP) in adult mice leads to anorexia and starvation within 7 d that is caused by hyperactivity of neurons within the parabrachial nucleus (PBN). Because NMDA glutamate receptors are involved in various synaptic plasticity-based behavioral modifications, we hypothesized that modulation of the NR2A and NR2B subunits of the NMDA receptor in PBN neurons could contribute to the anorexia phenotype. We observed by Western blot analyses that ablation of AgRP neurons results in enhanced expression of NR2B along with a modest suppression of NR2A. Interestingly, systemic administration of LiCl in a critical time window before AgRP neuron ablation abolished the anorectic response. LiCl treatment suppressed NR2B levels in the PBN and ameliorated the local Fos induction that is associated with anorexia. This protective role of LiCl on feeding was blunted in vagotomized mice. Chronic infusion of RO25-6981, a selective NR2B inhibitor, into the PBN recapitulated the role of LiCl in maintaining feeding after AgRP neuron ablation. We suggest that the accumulation of NR2B subunits in the PBN contributes to aphagia in response to AgRP neuron ablation and may be involved in other forms of anorexia.

    Topics: Adjuvants, Immunologic; Agouti-Related Protein; Animals; Anorexia; Appetite; Blotting, Western; Body Weight; Deglutition Disorders; Eating; Lithium Chloride; Male; Mice; Mice, Knockout; Neurons; Phenols; Piperidines; Pons; Receptors, N-Methyl-D-Aspartate; Rhombencephalon; Time Factors; Vagotomy

2013
Tolerance to hypophagia induced by prolonged treatment with a CB1 antagonist is related to the reversion of anorexigenic neuropeptide gene expression in the hypothalamus.
    Regulatory peptides, 2013, Mar-10, Volume: 182

    It is well established that treatment with rimonabant, a CB1 antagonist, decreases food intake and body weight gain. In part, these responses are mediated by increased activity of hypothalamic neurons related with energy homeostasis. However, food consumption is reversed to basal level during prolonged CB1 antagonist treatment, suggesting tolerance to its anorexigenic effect. This study investigated the effects of acute or prolonged CB1 receptor blockade on the expression of hypothalamic neuropeptides involved with energy homeostasis. Male Wistar rats received vehicle, a single dose or daily doses of rimonabant (10 mg/kg by gavage) over 7 days. Food intake, body weight, CRF and CART immunoreactivity, as well as, mRNA expression of hypothalamic neuropeptides were evaluated. In comparison with vehicle treatment, single dose of rimonabant decreased food intake and body weight. Acute rimonabant treatment also increased Fos-CRF and Fos-CART double labeled neurons in the PVN and Fos immunoreactivity in the ARC. We also observed that acute rimonabant treatment increased CRF, CART and TRH mRNA expression in the PVN, while it decreased POMC and NPY mRNA expression in the ARC with no changes in the CART mRNA expression in this nucleus. There was an increase in CB1 mRNA expression in the PVN of rats that received both acute and prolonged-rimonabant treatment. Interestingly, rats subjected to prolonged rimonabant treatment had no changes in food intake, body weight gain, hypothalamic mRNA expression, Fos expression and CRF and CART neuron activation. These data indicate that tolerance to hypophagic effects of CB1 antagonist, rimonabant, is associated with reversion of hypothalamic neuropeptide gene expression related to regulation of energy homeostasis.

    Topics: Adaptation, Physiological; Animals; Anorexia; Body Weight; Cannabinoid Receptor Antagonists; Eating; Hypothalamus; Male; Neuropeptides; Piperidines; Pyrazoles; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Rimonabant; RNA, Messenger

2013
The nucleus accumbens 5-HTR₄-CART pathway ties anorexia to hyperactivity.
    Translational psychiatry, 2012, Dec-11, Volume: 2

    In mental diseases, the brain does not systematically adjust motor activity to feeding. Probably, the most outlined example is the association between hyperactivity and anorexia in Anorexia nervosa. The neural underpinnings of this 'paradox', however, are poorly elucidated. Although anorexia and hyperactivity prevail over self-preservation, both symptoms rarely exist independently, suggesting commonalities in neural pathways, most likely in the reward system. We previously discovered an addictive molecular facet of anorexia, involving production, in the nucleus accumbens (NAc), of the same transcripts stimulated in response to cocaine and amphetamine (CART) upon stimulation of the 5-HT(4) receptors (5-HTR(4)) or MDMA (ecstasy). Here, we tested whether this pathway predisposes not only to anorexia but also to hyperactivity. Following food restriction, mice are expected to overeat. However, selecting hyperactive and addiction-related animal models, we observed that mice lacking 5-HTR(1B) self-imposed food restriction after deprivation and still displayed anorexia and hyperactivity after ecstasy. Decryption of the mechanisms showed a gain-of-function of 5-HTR(4) in the absence of 5-HTR(1B), associated with CART surplus in the NAc and not in other brain areas. NAc-5-HTR(4) overexpression upregulated NAc-CART, provoked anorexia and hyperactivity. NAc-5-HTR(4) knockdown or blockade reduced ecstasy-induced hyperactivity. Finally, NAc-CART knockdown suppressed hyperactivity upon stimulation of the NAc-5-HTR(4). Additionally, inactivating NAc-5-HTR(4) suppressed ecstasy's preference, strengthening the rewarding facet of anorexia. In conclusion, the NAc-5-HTR(4)/CART pathway establishes a 'tight-junction' between anorexia and hyperactivity, suggesting the existence of a primary functional unit susceptible to limit overeating associated with resting following homeostasis rules.

    Topics: Amphetamine; Animals; Anorexia; Cocaine; Hyperkinesis; Male; Mice; Mice, Knockout; N-Methyl-3,4-methylenedioxyamphetamine; Nucleus Accumbens; Piperidines; Propane; Real-Time Polymerase Chain Reaction; Receptors, Serotonin, 5-HT4; Serotonin 5-HT4 Receptor Antagonists

2012
Additive effects of cannabinoid CB1 receptors blockade and cholecystokinin on feeding inhibition.
    Pharmacology, biochemistry, and behavior, 2011, Volume: 98, Issue:2

    Cannabinoid CB1 receptor and cholecystokinin-1 (CCK(1)) receptors are located in peripheral nerve terminals of the gut, where they mediate satiety signals. Here we describe a detailed analysis of the interaction of both receptors in the control of feeding of food-deprived rats. Male Wistar rats were deprived for food 24h before testing. Rats were pre-treated with SR141716A (Rimonabant) or WIN 55,212-2 before CCK-8 sulphated administration and tested for food intake 60, 120 and 240 min after last drug injection. In parallel, the effect of Lorglumide--a CCK(1) receptor antagonist--pre-treatment was evaluated on feeding behaviour after SR141716A administration. Results show that SR141716A activates c-Fos expression in brainstem areas receiving vagal inputs. Blockade of CB1 receptors with SR141716A (1 mg/kg) reduces feeding and display additive satiety induction with the CCK(1) receptor agonist CCK-8 sulphated (5, 10, 25 μg/kg). The effect of SR141716A is not blocked by Lorglumide (10 mg/kg), indicating independent sites of action. Conversely, the administration of the CB1 agonist WIN 55,212-2 (2 mg/kg) reduced satiety induced by CCK-8. In conclusion, these results report additive anorectic actions for CCK1 activation and peripheral CB1 receptor blockade providing a framework for combined therapies in the treatment of eating disorders.

    Topics: Animals; Anorexia; Benzoxazines; Brain; Drug Synergism; Feeding Behavior; Gene Expression; Genes, fos; Male; Morpholines; Naphthalenes; Piperidines; Proglumide; Pyrazoles; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Receptor, Cholecystokinin B; Rimonabant; Sincalide

2011
Activation of ERα is necessary for estradiol's anorexigenic effect in female rats.
    Hormones and behavior, 2010, Volume: 58, Issue:5

    While there is considerable evidence that the ovarian hormone estradiol reduces food intake in female rats, it is unclear which estrogen receptor (ER) subtype, ERα or ERβ, mediates this effect. While several studies have demonstrated that activation of ERα, but not ERβ, is sufficient to reduce food intake in ovariectomized (OVX) rats, there are limited data regarding which receptor subtype is necessary. Here we used the selective ERα and ERß antagonists, MPrP and PHTPP, respectively, to investigate this question. We found that antagonism of ERα, but not ERβ, prevented the decrease in food intake following acute administration of estradiol in OVX rats. In addition, antagonism of ERα prevented the estrous-related, phasic reduction in food intake that occurs in response to the rise in circulating levels of estradiol in cycling rats. We conclude that activation of ERα is necessary for the anorexigenic effects of exogenous and endogenous estradiol in female rats.

    Topics: Animals; Anorexia; Appetite Depressants; Drug Evaluation, Preclinical; Eating; Estradiol; Estrogen Receptor alpha; Female; Ovariectomy; Piperidines; Pyrazoles; Pyrimidines; Rats; Rats, Long-Evans; Selective Estrogen Receptor Modulators

2010
Rimonabant induced anorexia in rodents is not mediated by vagal or sympathetic gut afferents.
    Neuroscience letters, 2009, Jan-02, Volume: 449, Issue:1

    The selective CB1 receptor antagonist rimonabant is a novel weight control agent. Although CB1 receptors and binding sites are present in both the rodent central and peripheral nervous systems, including the afferent vagus nerve, the role of gut afferents in mediating anorexia following CB1R blockade is still debated. In the present study we examined rimonabant-induced anorexia in male C57BL/6J mice with subdiaphragmatic vagotomy (VGX) as well as in male Sprague-Dawley rats subjected to either subdiaphragmatic vagal deafferentation (SDA) alone or in combination with a complete celiac-superior mesenteric ganglionectomy (CGX). Irrespective of the operational procedure, rimonabant (10mg/kg) effectively reduced standard chow as well as palatable diet (ensure) intake. In conclusion, the data clearly demonstrate that neither vagal gut afferents, nor gut afferents traveling via the sympathetic nervous system, are required for rimonabant to inhibit food intake leading to the hypothesis that centrally located CB1 receptors are the prime mediators of rimonabant-induced anorexia.

    Topics: Analysis of Variance; Animals; Anorexia; Eating; Ganglia, Sympathetic; Ganglionectomy; Male; Mice; Mice, Inbred C57BL; Piperidines; Pyrazoles; Rats; Rats, Sprague-Dawley; Rimonabant; Stilbamidines; Vagotomy; Vagus Nerve

2009
Responses of hypothalamo-pituitary-adrenal axis to a cholinesterase inhibitor.
    Neuroreport, 2009, Oct-07, Volume: 20, Issue:15

    Acute gastrointestinal events (mostly manifested by nausea, vomiting, or loss of appetite) are class effects of all cholinesterase inhibitors, which are prescribed for the treatment of Alzheimer's disease. The underlying mechanism, however, has been unclear. Because corticotropin-releasing hormone is related to appetite control, we focused on the activation of the hypothalamo-pituitary-adrenal system and food intake following the administration of the cholinesterase inhibitor, donepezil, in rats. We monitored the plasma concentrations of adrenocorticotropic hormone, c-Fos, in the paraventricular nucleus, and intakes of rat chow for 3 h after the first administration of donepezil, and 2 weeks later, after daily administration of donepezil. The intragastric administration of 3 mg/kg of donepezil significantly increased the plasma adrenocorticotropic hormone levels and c-Fos expression in the paraventricular nucleus, and decreased the food intake on the first day. The increase in adrenocorticotropic hormone and loss of appetite after oral administration of the drug were attenuated after daily administration for 2 weeks.

    Topics: Adrenocorticotropic Hormone; Animals; Anorexia; Appetite; Appetite Regulation; Cholinesterase Inhibitors; Donepezil; Drug Administration Schedule; Hypothalamo-Hypophyseal System; Indans; Male; Neurosecretory Systems; Paraventricular Hypothalamic Nucleus; Piperidines; Pituitary-Adrenal System; Proto-Oncogene Proteins c-fos; Rats; Rats, Wistar; Up-Regulation

2009
Grooming, scratching and feeding: role of response competition in acute anorectic response to rimonabant in male rats.
    Psychopharmacology, 2007, Volume: 195, Issue:1

    Although the CB1 receptor antagonist/inverse agonist rimonabant acutely suppresses food intake in rodents, the behavioural specificity of this effect remains unclear.. To profile the behavioural effects of rimonabant in a free-feeding context.. Videoanalysis was employed to characterise the effects of acute rimonabant (1.5 and 3.0 mg/kg, IP) on the behaviour of non-deprived male rats exposed to palatable mash. Data were also collected on post-treatment weight gain, and, as prolonged appetite suppression has been found after single dosing with compounds of this series, rats were reassessed (drug-free) for food intake 7 days after initial testing.. Both doses of rimonabant not only decreased mash consumption (44-55%) but also reduced 24-h weight gain. Although videoanalysis confirmed the inhibitory effects of rimonabant on feeding behaviour, it also revealed concurrent reductions in locomotion, rearing and sniffing as well as substantial (up to tenfold) and dose-dependent increases in grooming and scratching. Timecourse analyses further revealed that rimonabant dose-dependently induced frequent episodes of atypical scratching that waned over the test but which were succeeded by prolonged and behaviourally disruptive grooming. Finally, as groups did not differ in mash consumption on retest, any prolonged anorectic effect of acute rimonabant dissipates within 7 days of treatment.. The anorectic response to rimonabant in male rats would appear to be due largely to response competition. This parsimonious conclusion is supported by the less profound (although still significant) increases in scratching and grooming observed in rats treated with a sub-anorectic dose (0.5 mg/kg) of the compound.

    Topics: Animals; Anorexia; Data Interpretation, Statistical; Dose-Response Relationship, Drug; Eating; Feeding Behavior; Grooming; Habituation, Psychophysiologic; Injections, Intraperitoneal; Male; Piperidines; Pruritus; Pyrazoles; Rats; Receptor, Cannabinoid, CB1; Rest; Rimonabant; Satiety Response; Time Factors; Videotape Recording; Weight Gain

2007
The selective estrogen receptor modulator acolbifene reduces cholesterolemia independently of its anorectic action in control and cholesterol-fed rats.
    The Journal of nutrition, 2005, Volume: 135, Issue:9

    The cancer-preventing selective estrogen receptor modulator (SERM) acolbifene (ACOL) exerts a potent and pure antiestrogenic action in the mammary gland and uterus, yet it displays beneficial, estrogen-like actions on energy and lipid metabolism in rodents. The compound reduces food intake and strongly decreases cholesterolemia in rats fed a cholesterol-free diet. This study was designed to establish whether the anorectic effect of ACOL is involved in its cholesterol-lowering action, and whether the compound retains its ability to lower cholesterol concentrations in rats with diet-induced hypercholesterolemia. Female rats were fed a purified diet devoid of cholesterol (reference diet) or containing 2% cholesterol (C-diet); they were either not treated or treated daily with ACOL or not treated and pair-fed to the ACOL-treated rats. The C-diet did not affect food intake or weight and fat gains. ACOL reduced food intake (16%) and weight gain (45%, mainly fat) similarly in both dietary cohorts. ACOL, but not pair feeding, reduced cholesterolemia by 33% in rats fed the reference diet. As expected, the C-diet raised serum total cholesterol almost 3-fold and this increase was largely prevented by ACOL but not by pair feeding. Cholesterol was reduced by ACOL, mainly in the HDL fraction, in rats fed the reference diet, but only in the non-HDL fraction in those fed the C-diet. In livers of rats fed the reference diet, ACOL, but not pair feeding, increased protein abundance of the scavenger receptor, class B, type 1, and the LDL receptor, thought to be involved in ACOL-mediated cholesterol lowering. These findings demonstrate that the potent hypocholesterolemic action of ACOL is independent of the concomitant reduction in food intake and fat accretion, and that such action occurs in rats with overt diet-induced hypercholesterolemia.

    Topics: Animals; Anorexia; Cholesterol; Cholesterol, Dietary; Female; Hypercholesterolemia; Liver; Piperidines; Rats; Rats, Sprague-Dawley; Receptors, LDL; Scavenger Receptors, Class B; Selective Estrogen Receptor Modulators

2005
[Feeding disorders in 5-HT4 receptor knockout mice].
    Journal de la Societe de biologie, 2004, Volume: 198, Issue:1

    To study the functional contributions of the 5-HT4 receptor subtype of serotonin (5-HT), we have generated knockout mice lacking the 5-HT4 receptor gene. The male mutant mice exhibit a hyposensitivity to anorexic stress. Our recent data indicate that the pharmacological inactivation, using a systemic injection of the 5-HT4 receptor antagonist RS39604 (0.5 mg/kg), suppressed restraint stress-induced anorexia in wild-type female mice. In parallel, the same treatment reduced the 3,4-N-methylenedioxymethamphetamine (" ecstasy", 10 mg/kg)-induced anorexia in male wild-type mice. Our neurochemical analyses suggest that the mechanisms underlying feeding disorders in 5-HT4 receptor knockout mice are related to a lesser efficacy of 5-HT (hypothalamus, nucleus accumbens), leptin and the cocaine-amphetamine related transcript to reduce food intake following stress.

    Topics: Animals; Anorexia; Appetite; Chromatography, High Pressure Liquid; Corticosterone; Feeding and Eating Disorders; Gene Expression Regulation; Leptin; Limbic System; Male; Mice; Mice, Knockout; N-Methyl-3,4-methylenedioxyamphetamine; Nerve Tissue Proteins; Piperidines; Propane; Receptors, Serotonin, 5-HT4; Restraint, Physical; Reverse Transcriptase Polymerase Chain Reaction; Serotonin; Serotonin 5-HT4 Receptor Antagonists; Serotonin Antagonists; Stress, Psychological

2004
Histamine H1 receptors mediate the anorectic action of the pancreatic hormone amylin.
    American journal of physiology. Regulatory, integrative and comparative physiology, 2001, Volume: 281, Issue:5

    We investigated the role of histamine H1 receptors in mediating the anorectic effect of intraperitoneally injected amylin (5 and 20 microg/kg), the amylin agonist salmon calcitonin (sCT; 10 microg/kg), leptin (1.3 mg/kg), and cholecystokinin (CCK; 20 microg/kg). The experiments were performed with mice lacking functional H1 receptors (H1Rko) and wild-type (WT) controls. The mice were also injected with the H3 antagonist thioperamide (20 mg/kg), which reduces feeding by enhancing the release of endogenous histamine through presynaptic H3 receptors. The feeding-suppressive effect of thioperamide was abolished in H1Rko mice. The anorectic effects of amylin and sCT were significantly reduced in 12-h food-deprived H1Rko mice compared with WT mice [1-h food intake: WT-NaCl 0.51 +/- 0.05 g vs. WT-amylin (5 microg/kg) 0.30 +/- 0.06 g (P < 0.01); H1Rko-NaCl 0.45 +/- 0.05 g vs. H1Rko-amylin 0.40 +/- 0.04 g; WT-NaCl 0.40 +/- 0.09 g vs. WT-sCT (10 microg/kg) 0.14 +/- 0.10 g (P < 0.05); H1Rko-NaCl 0.44 +/- 0.08 g vs. H1Rko-sCT 0.50 +/- 0.06 g]. The anorectic effect of leptin was absent in ad libitum-fed H1Rko mice, whereas CCK equally reduced feeding in WT and H1Rko animals. This suggests that the histaminergic system is involved in mediating the anorectic effects of peripheral amylin and sCT via histamine H1 receptors. The same applies to leptin but not to CCK. H1Rko mice showed significantly increased body weight gain compared with WT mice, supporting the role of endogenous histamine in the regulation of feeding and body weight.

    Topics: Amyloid; Animals; Anorexia; Body Weight; Calcitonin; Cholecystokinin; Eating; Histamine Antagonists; Islet Amyloid Polypeptide; Leptin; Male; Mice; Mice, Knockout; Pancreas; Piperidines; Receptors, Histamine H1

2001
NMDA receptor antagonists potently suppress the spontaneous withdrawal signs induced by discontinuation of long-term diazepam treatment in Fischer 344 rats.
    Brain research, 1998, Apr-20, Volume: 790, Issue:1-2

    The present study investigated the effects of the NMDA receptor antagonists dizocilpine (MK-801) and ifenprodil on the appearance of diazepam withdrawal signs caused by discontinuation of long-term diazepam treatment using a drug-admixed food (DAF) method in Fischer 344 rats. The total withdrawal score was significantly decreased by after-withdrawal treatment with dizocilpine or ifenprodil. Dizocilpine, in particular, markedly suppressed the motor withdrawal signs and body weight loss, while ifenprodil suppressed the motor and emotional withdrawal signs. Furthermore, the decrease in the food intake during withdrawal (anorexia) was significantly reduced by dizocilpine, but not by ifenprodil. These behavioral results indicated that the activation of NMDA receptors during withdrawal may play an important role in the appearance of withdrawal signs (in particular motor withdrawal signs) caused by discontinuation of chronic diazepam treatment, and that inhibitory agents for NMDA receptors may be effective in alleviation of the appearance of benzodiazepine withdrawal signs.

    Topics: Administration, Oral; Animals; Anorexia; Anti-Anxiety Agents; Behavior, Animal; Diazepam; Dizocilpine Maleate; Eating; Emotions; Excitatory Amino Acid Antagonists; Male; Motor Activity; Piperidines; Rats; Rats, Inbred F344; Receptors, N-Methyl-D-Aspartate; Substance Withdrawal Syndrome; Time Factors; Weight Loss

1998
Effect of the 5HT2 antagonist ritanserin on food intake and on 5HT-induced anorexia in the rat.
    Pharmacology, biochemistry, and behavior, 1987, Volume: 26, Issue:2

    The present study investigated the effect on the rat's eating behavior of the new selective 5HT2 antagonist ritanserin. The results obtained indicate that: single subcutaneous (SC) injection of ritanserin, at doses between 0.1 and 1 mg/kg b.wt., neither elicits food intake in sated rats, nor increases the intake induced by food deprivation; subchronic SC treatment (15 days) with 0.1 mg/kg does not increase food intake nor body weight gain; subchronic SC treatment with high doses, 1 or 10 mg/kg, produces small and transient increases in food intake without affecting body weight gain. When ritanserin was tested for its ability to block the anorectic effect of exogenous 5HT, it inhibited the effect of intraperitoneal (IP) 5HT, but proved to be completely inactive versus the effect of 5HT injected into the hypothalamic paraventricular nucleus, which is highly sensitive to this effect of 5HT. This last finding suggests that the anorectic action of central endogenous 5HT is also not blocked by ritanserin, thus proposing a reasonable explanation for the absence of orexigenic effect following its administration. Moreover, it suggests that in rats the hypothalamic receptors mediating the effect of 5HT on eating behavior are different from the 5HT2 of the frontal cortex which have been shown to be completely blocked by ritanserin under the experimental conditions employed in our study.

    Topics: Animals; Anorexia; Brain; Drinking Behavior; Feeding and Eating Disorders; Feeding Behavior; Food Deprivation; Male; Piperidines; Rats; Rats, Inbred Strains; Ritanserin; Satiation; Serotonin; Serotonin Antagonists

1987
Further studies on the mechanism of serotonin-dependent anorexia in rats.
    Psychopharmacology, 1980, Volume: 68, Issue:1

    4-(3-Indolyl-2-ethyl) piperidine (LM 5008), 2-(1-piperazinyl) quinoline (quipazine), and metachlorophenylpiperazine (mCPP) were studied for their ability to affect serotonergic mechanisms in vitro. Their relative potency in inhibiting serotonin (5-HT) uptake in vivo and reducing food intake in rats was also examined. mCPP was very potent in displacing 3H-5-HT bound to brain membranes (IC50, 6.2 X 10(-7) M), followed by quipazine, which showed an IC50 of 3.8 X 10(-6) M. LM 5008 was the least effective with an IC50 of 3.6 X 10(-5) M. mCPP and quipazine were less potent than d-fenfluramine in releasing 14C-5-HT from brain synaptosomes, while LM 5008 caused no significant effects at a concentration of 10(-5) M. Conversely, both in vitro and in vivo studies on 5-HT uptake showed that LM 5008 was the most potent compound in inhibiting 5-HT uptake and mCPP the least potent. Since a 50% reduction of food intake was not reached even with a dose of LM 5008 27-times higher than the ED50 for inhibiting 5-HT uptake in vivo, it is suggested that even marked inhibition of 5-HT uptake at central synapses is not sufficient per se to trigger serotonin-dependent anorexia in the rat. Increased release and/or direct stimulation of post-synaptic receptors may be necessary to obtain this effect. This could be of interest for developing new agents which can cause anorexia by interacting with brain serotonin.

    Topics: Animals; Anorexia; Brain; Feeding and Eating Disorders; Feeding Behavior; Female; Fenfluramine; Humans; Piperazines; Piperidines; Quipazine; Rats; Serotonin; Serotonin Antagonists; Synaptosomes; Time Factors

1980
Evidence that it is possible to cause anorexia by increasing release and/or directly stimulating postsynaptic serotonin receptors in the brain.
    Progress in neuro-psychopharmacology, 1980, Volume: 4, Issue:4-5

    Topics: Animals; Anorexia; Appetite Depressants; Brain; Feeding Behavior; Fenfluramine; Piperazines; Piperidines; Quipazine; Rats; Receptors, Serotonin; Serotonin; Synaptosomes

1980