piperidines and Anorexia-Nervosa

Anorexia nervosa is a serious, multifactorial disease, characterized by psychiatric and neurological disturbances, which would appear to be similar to the manifestations of dementia. Patients with anorexia nervosa present compromised affectivity, characterized by hypomanic, manic and depressive symptoms, and their cholinergic system is altered with a decrease in the release of acetylcholine. Donepezil is a drug that been proven to be effective in the treatment of dementia, including Alzheimer's; it has been used for affective disorders and its mechanism of action is to inhibit the acetylcholinesterase enzyme to increase acetylcholine. Therefore, donepezil could be effective in treating anorexia nervosa.

Topics: Animals; Anorexia Nervosa; Donepezil; Humans; Indans; Piperidines; Treatment Outcome

Topics: Anemia, Pernicious; Anorexia Nervosa; Cisapride; Connective Tissue Diseases; Diabetes Complications; Domperidone; Drug-Related Side Effects and Adverse Reactions; Gastric Emptying; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Intestinal Pseudo-Obstruction; Metoclopramide; Piperidines; Postgastrectomy Syndromes; Stomach Diseases

Indirect estimations of brain neurotransmitters in patients with anorexia nervosa (AN) and low weight have demonstrated a reduction in brain serotonin (5-HT) turnover in general and led to hypotheses about dysfunction in the 5-HT(2a) receptor system. It was our aim to investigate the central 5-HT(2a) receptor binding index using SPECT brain imaging.. The 5-HT(2a) receptors of low-weight patients with AN were studied by means of the highly specific radioiodinated 5-HT(2a) receptor antagonist 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide or (123)I-5-I-R91150. Fifteen patients with clinical diagnoses of AN and 11 age-matched healthy volunteers received intravenous injections of 185 MBq (123)I-5-I-R91150 and were scanned with high-resolution brain SPECT.. Compared with healthy volunteers, patients with AN had a significantly reduced 5-HT(2a) binding index in the left frontal cortex, the left and right parietal cortex, and the left and right occipital cortex. A significant left-right asymmetry was noted in the frontal cortex (left < right).. These results are in accordance with diminished metabolic and perfusion of frontal and parietal cortices reported in recent neuroimaging studies and imply localized disturbed serotonergic function. The data are discussed in the light of possible confounding factors related to the low-weight AN status. A regional cortical reduction in 5-HT(2a) binding index is not likely to be caused by a general reduction in serotonergic function due to the possible confounding factors. Suggestions for further research are given.

Topics: Adolescent; Adult; Anorexia Nervosa; Cerebral Cortex; Female; Frontal Lobe; Humans; Iodine Radioisotopes; Male; Occipital Lobe; Parietal Lobe; Piperidines; Radiopharmaceuticals; Receptor, Serotonin, 5-HT2A; Receptors, Serotonin; Tissue Distribution; Tomography, Emission-Computed, Single-Photon

To determine the efficacy of cisapride, 10 mg three times daily, in improving gastric emptying, reducing distress during meals, and facilitating weight gain in anorexia nervosa, we conducted an 8-week, randomized, double-blind, placebo-controlled trial on 29 inpatients. Measures included scintigraphic gastric emptying studies at 0, 2, 4, and 8 weeks; subjective distress during meals measured by visual analogue scales; self-rating of degree of global improvement in symptoms associated with eating at end of study; and weight measured weekly. Gastric emptying improved significantly but equally in both groups over the study period. Yet subjective measures were better in the cisapride group; they rated themselves as more hungry (p = .02) and more improved on the global measure of change in symptoms (p = .02). Even so, the cisapride group did not gain more weight. The correlation between gastric emptying and weight gain was modest (r = .30; p = .11), and between gastric emptying and the subjective measures, virtually absent.

Topics: Adolescent; Adult; Anorexia Nervosa; Cisapride; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Gastric Emptying; Humans; Pain Measurement; Piperidines; Serotonin Antagonists; Treatment Outcome; Weight Gain

In a double-blind trial, 12 out-patients with primary anorexia nervosa received, for six weeks, either 10 mg cisapride or placebo, three times a day. Cisapride accelerated gastric emptying of a radiolabelled semisolid meal in all six patients; five gained weight and symptoms of gastric retention ameliorated in four. With placebo, three of six had emptying enhanced, four gained weight, and one's symptoms improved. For another six weeks, all patients received cisapride. In five of the patients who had received cisapride, emptying further accelerated or remained stable; in one it slowed. Of the six patients who received placebo, four had emptying accelerated, five gained weight, and symptoms improved in four. Longer administration of cisapride may, by enhancing gastric motor activity, alleviate symptoms of retention and thus help to change eating behaviour.

Topics: Adult; Anorexia Nervosa; Body Weight; Cisapride; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Eating; Female; Follow-Up Studies; Gastric Emptying; Humans; Long-Term Care; Piperidines; Serotonin Antagonists

Delayed gastric emptying is common in primary anorexia nervosa. We investigated in 12 patients whether gastric emptying could be accelerated by the prokinetic drug cisapride. Patients were studied on two occasions 1 wk apart and received, under random double-blind conditions, 8 mg of cisapride and placebo intravenously. Gastric emptying of an isotopically labeled semisolid meal and antral motor activity were measured using a dual-headed gamma-camera for 50 min. Emptying was significantly slower (half-emptying time, 50-191 min; median, 121 min) than in 24 healthy volunteers (half-emptying times, 21-119 min; median, 47 min). Cisapride accelerated emptying significantly (p less than 0.001; half-emptying time after cisapride, 22-80 min; median, 42 min). Antral contraction amplitude increased and contraction frequency decreased significantly (p less than 0.001), whereas the propagation velocity of contractions remained unchanged. We concluded that intravenous cisapride accelerates gastric emptying and increases antral contraction amplitude in patients with anorexia nervosa. Whether or not these effects can prove beneficial in diminishing the patients' symptoms and in helping them to gain weight can only be answered from studies involving long-term treatment with cisapride.

Topics: Adolescent; Adult; Anorexia Nervosa; Cisapride; Drug Evaluation; Female; Gastric Emptying; Humans; Injections, Intravenous; Muscle Contraction; Piperidines; Pyloric Antrum; Radionuclide Imaging; Technetium Tc 99m Sulfur Colloid; Time Factors

This hypothesis is that patients with anorexia nervosa (AN) demonstrate derangement in the histamine central nervous system. It might be possible to ameliorate these by careful use of histamine receptor antagonists targeting Histamine 1, 2, or 3 receptors. Histamine 3 receptors are exclusively present in the brain. Pitolisant is the only one agent currently available that targets these receptors. Pitolisant (brand name Wakix) was approved in the European Union, as a treatment for narcolepsy in March 2016.

Topics: Alcoholism; Animals; Anorexia Nervosa; Behavior, Animal; Brain; Central Nervous System; Dietary Fats; Endocannabinoids; Female; Hibernation; Hippocampus; Histamine; Histamine Antagonists; Humans; Male; Piperidines; Prader-Willi Syndrome; Rats; Receptors, Histamine H1; Receptors, Histamine H2; Receptors, Histamine H3; Sex Factors

Anorexia nervosa (AN) is an eating disorder characterized by severe hypophagia and weight loss, and an intense fear of weight gain. Activity-based anorexia (ABA) refers to the weight loss, hypophagia and paradoxical hyperactivity that develops in rodents exposed to running wheels and restricted food access, and provides a model for aspects of AN. The atypical antipsychotic olanzapine was recently shown to reduce both AN symptoms and ABA. We examined which component of the complex pharmacological profile of olanzapine reduces ABA. Mice received 5-HT(2A/2C), 5-HT3, dopamine D1-like, D2, D3 or D2/3 antagonist treatment, and were assessed for food intake, body weight, wheel running and survival in ABA. D2/3 receptor antagonists eticlopride and amisulpride reduced weight loss and hypophagia, and increased survival during ABA. Furthermore, amisulpride produced larger reductions in weight loss and hypophagia than olanzapine. Treatment with either D3 receptor antagonist SB277011A or D2 receptor antagonist L-741,626 also increased survival. All the other treatments either had no effect or worsened ABA. Overall, selective antagonism of D2 and/or D3 receptors robustly reduces ABA. Studies investigating the mechanisms by which D2 and/or D3 receptors regulate ABA, and the efficacy for D2/3 and/or D3 antagonists to treat AN, are warranted.

Topics: Amisulpride; Animals; Anorexia Nervosa; Benzodiazepines; Disease Models, Animal; Dopamine D2 Receptor Antagonists; Eating; Female; Indoles; Mice; Mice, Inbred BALB C; Motor Activity; Nitriles; Olanzapine; Piperidines; Receptors, Dopamine D3; Salicylamides; Sulpiride; Tetrahydroisoquinolines; Weight Loss

It is well known that endocannabinoids play an important role in the regulation of food intake and body weight. Endocannabinoids and cannabinoid receptors are found in the hypothalamus and brainstem, which are central areas involved in the control of food intake and energy expenditure. Activation of these areas is related to hypophagia observed during inflammatory stimulus. This study investigated the effects of cannabinoid (CB₁) receptor blockade on lipopolysaccharide (LPS)-induced hypophagia. Male Wistar rats were pretreated with rimonabant (10 mg/kg, by gavage) or vehicle; 30 min later they received an injection of either LPS (100 μg/kg, intraperitoneal) or saline. Food intake, body weight, corticosterone response, CRF and CART mRNA expression, Fos-CRF and Fos-α-MSH immunoreactivity in the hypothalamus and Fos-tyrosine hydroxylase (TH) immunoreactivity in the brainstem were evaluated. LPS administration decreased food intake and body weight gain and increased plasma corticosterone levels and CRF mRNA expression in the PVN. We also observed an increase in Fos-CRF and Fos-TH double-labeled neurons after LPS injection in vehicle-pretreated rats, with no changes in CART mRNA or Fos-α-MSH immunoreactive neurons in the ARC. In saline-treated animals, rimonabant pretreatment decreased food intake and body weight gain but did not modify hormone response or Fos expression in the hypothalamus and brainstem compared with vehicle-pretreated rats. Rimonabant pretreatment potentiated LPS-induced hypophagia, body weight loss and Fos-CRF and Fos-TH expressing neurons. Rimonabant did not modify corticosterone, CRF mRNA or Fos-α-MSH responses in rats treated with LPS. These data suggest that the endocannabinoid system, mediated by CB₁ receptors, modulates hypothalamic and brainstem circuitry underlying the hypophagic effect during endotoxemia to prevent an exaggerated food intake decrease. This article is part of a Special Issue entitled 'Central Control of Food Intake'.

Topics: Animals; Anorexia Nervosa; Body Weight; Brain Stem; Cell Count; Corticosterone; Corticotropin-Releasing Hormone; Disease Models, Animal; Eating; Endotoxemia; Gene Expression Regulation; Hypothalamus; Lipopolysaccharides; Male; Melanocyte-Stimulating Hormones; Microdialysis; Neurons; Oncogene Proteins v-fos; Piperidines; Pyrazoles; Radioimmunoassay; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Rimonabant; RNA, Messenger; Time Factors; Tyrosine 3-Monooxygenase

Topics: Adult; Anorexia Nervosa; Body Image; Body Weight; Cisapride; Dyspepsia; Female; Gastric Emptying; Hong Kong; Humans; Piperidines; Serotonin Antagonists; Somatoform Disorders