piperidines and Bulimia

1. Brofaromine or placebo were administered to female bulimia nervosa patients over a period of eight weeks. Plasma and urinary trace amines, their acidic metabolites and the acidic metabolites of the catecholamines and serotonin were assessed prior to treatment and at four and eight weeks after commencement of treatment. 2. The levels of both plasma and urinary homovanillic and vanilmandelic acids declined significantly during the first four weeks of treatment with brofaromine and then partially recovered to pre-drug levels by the eighth week. 5-Hydroxyindoleacetic acid levels were not affected by drug treatment at the times assessments were made. Urinary tryptamine increased significantly during the first four weeks of brofaromine treatment then partially recovered towards pre-drug levels by the eighth week. No effect from placebo treatment was observed.

Topics: Biogenic Amines; Bulimia; Double-Blind Method; Female; Homovanillic Acid; Humans; Hydroxyindoleacetic Acid; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Piperidines; Tryptamines; Vanilmandelic Acid

Brofaromine, a selective and reversible inhibitor of monoamine oxidase-A (MAO-A) was given to 19 women while 17 received placebo for 8 weeks. All met DSM III-R criteria for bulimia nervosa, a psychiatric disorder in which uncontrolled overeating episodes are accompanied by purging activities and extreme concerns about body shape and weight. The following indices were measured: plasma and urinary phenylacetic acid (PAA), homovanillic acid (HVA), vanillylmandellic acid (VMA); plasma tryptamine (T), beta phenylethylamine (PE), and 5-hydroxyindoleacetic acid (5-HIAA) and urinary 6-sulphatoxymelatonin (aMT6s). PE levels remained the same but T showed a trend toward elevation over time. Twenty-four hour levels of urinary aMT6s in BN patients were higher at week 4 when compared to baseline and week 8. There was a significant reduction in plasma VMA and HVA over time during treatment with brofaromine and both plasma HVA and VMA were significantly lower for the brofaromine group compared to placebo at week 4. Plasma 5-HIAA was significantly higher for the brofaromine group after 8 weeks when compared to placebo. Urinary VMA decreased significantly from baseline to week 4 with a partial elevation at 8 weeks. Urinary VMA was also significantly lower in patients on brofaromine at week 4. This study verifies that brofaromine complies with predicted MAO-A inhibiting patterns in a clinical population.

Topics: Adolescent; Adult; Biogenic Amines; Bulimia; Female; Homovanillic Acid; Humans; Hydrogen-Ion Concentration; Hydroxyindoleacetic Acid; Melatonin; Monoamine Oxidase Inhibitors; Piperidines; Tryptamines; Vanilmandelic Acid

Pharmacologic and cognitive behavioral therapies have been advocated in the treatment of bulimia nervosa (BN). Brofaromine, a selective and reversible inhibitor of monoamine oxidase-A was selected for a double-blind, placebo-controlled evaluation because of previous demonstrated monoamine oxidase inhibitor efficacy in BN and because of its safer adverse reaction profile. Thirty-six female patients who met DSM-III-R criteria for BN were randomly assigned to the drug group (N = 19) or to the placebo group (N = 17) for an 8-week outpatient trial. Brofaromine produced a significant effect in decreasing episodes of vomiting throughout the trial, although comparable reductions in episodes of binge eating were found in both groups. Also, there were no advantages of drug over placebo on improvements in attitudinal measures and shape or on self-report ratings of depression and anxiety. However, a significant proportion of the subjects on brofaromine lost weight when compared with the placebo group. Methodologic issues including subjective assessment measures, placebo response rates, and the elucidation of responder subgroups are discussed.

Topics: Adolescent; Adult; Affect; Attitude; Body Image; Body Weight; Bulimia; Double-Blind Method; Feeding Behavior; Female; Humans; Monoamine Oxidase Inhibitors; Piperidines; Psychiatric Status Rating Scales; Vomiting

The enantiomers of the potent σ

Topics: Animals; Binge-Eating Disorder; Bulimia; Female; Guinea Pigs; Humans; Isomerism; Piperidines; Rats; Rats, Sprague-Dawley; Receptors, sigma; Sigma-1 Receptor; Spiro Compounds; Structure-Activity Relationship

Binge-eating disorder (BED) is characterized by recurring episodes of excessive consumption of palatable food and an increased sensitivity to food cues. Patients with BED display an addiction-like symptomatology and the dopamine system might be a potential treatment target. The clinically safe monoamine stabilizer (-)-OSU6162 (OSU6162) restores dopaminergic dysfunction in long-term alcohol-drinking rats and shows promise as a novel treatment for alcohol use disorder. Here, the effects of OSU6162 on consummatory (binge-like eating) and appetitive (cue-controlled seeking) behavior motivated by chocolate-flavored sucrose pellets were evaluated in non-food-restricted male Lister Hooded rats. OSU6162 significantly reduced binge-like intake of chocolate-flavored sucrose pellets without affecting prior chow intake. Furthermore, OSU6162 significantly reduced the cue-controlled seeking of chocolate-flavored sucrose pellets under a second-order schedule of reinforcement before, but not after, the delivery and ingestion of reward, indicating a selective effect on incentive motivational processes. In contrast, the dopamine D2/D3 receptor antagonist raclopride reduced the seeking of chocolate-flavored sucrose pellets both pre- and post reward ingestion and also reduced responding under simpler schedules of seeking behavior. The D1/5 receptor antagonist SCH23390 had no effect on instrumental behavior under any reinforcement schedule tested. Finally, local administration of OSU6162 into the nucleus accumbens core, but not dorsolateral striatum, selectively reduced cue-controlled sucrose seeking. In conclusion, the present results show that OSU6162 reduces binge-like eating behavior and attenuates the impact of cues on seeking of palatable food. This indicates that OSU6162 might serve as a novel BED medication.

Topics: Animals; Appetitive Behavior; Benzazepines; Binge-Eating Disorder; Bulimia; Conditioning, Operant; Cues; Dietary Sucrose; Dose-Response Relationship, Drug; Feeding Behavior; Male; Neurotransmitter Agents; Nucleus Accumbens; Piperidines; Raclopride; Rats; Reward

Binge eating is a dysregulated form of feeding behavior that occurs in multiple eating disorders including binge-eating disorder, the most common eating disorder. Feeding is a complex behavioral program supported through the function of multiple brain regions and influenced by a diverse array of receptor signaling pathways. Previous studies have shown the overexpression of the opioid neuropeptide nociceptin (orphanin FQ, N/OFQ) can induce hyperphagia, but the role of endogenous nociceptin receptor (NOP) in naturally occurring palatability-induced hyperphagia is unknown. In this study we adapted a simple, replicable form of binge eating of high fat food (HFD). We found that male and female C57BL/6J mice provided with daily one-hour access sessions to HFD eat significantly more during this period than those provided with continuous 24h access. This form of feeding is rapid and entrained. Chronic intermittent HFD binge eating produced hyperactivity and increased light zone exploration in the open field and light-dark assays respectively. Treatment with the potent and selective NOP antagonist SB 612111 resulted in a significant dose-dependent reduction in binge intake in both male and female mice, and, unlike treatment with the serotonin selective reuptake inhibitor fluoxetine, produced no change in total 24-h food intake. SB 612111 treatment also significantly decreased non-binge-like acute HFD consumption in male mice. These data are consistent with the hypothesis that high fat binge eating is modulated by NOP signaling and that the NOP system may represent a promising novel receptor to explore for the treatment of binge eating.

Topics: Adaptation, Ocular; Analysis of Variance; Animals; Antidepressive Agents, Second-Generation; Bulimia; Cycloheptanes; Diet, High-Fat; Disease Models, Animal; Dose-Response Relationship, Drug; Exploratory Behavior; Female; Fluoxetine; Male; Maze Learning; Mice; Mice, Inbred C57BL; Nociceptin Receptor; Piperidines; Receptors, Opioid; Sex Characteristics; Time Factors

Positive reinforcement (e.g., appetitive, rewarding properties) has often been hypothesized to maintain excessive intake of palatable foods. Recently, rats receiving intermittent access to high sucrose diets showed binge-like intake with withdrawal-like signs upon cessation of access, suggesting negative reinforcement mechanisms contribute as well. Whether intermittent access to high fat diets also produces withdrawal-like syndromes is controversial. The present study therefore tested the hypothesis that binge-like eating and withdrawal-like anxiety would arise in a novel model of binge eating based on daily 10-min access to a sweet fat diet (35% fat kcal, 31% sucrose kcal). Within 2-3 weeks, female Wistar rats developed binge-like intake comparable to levels seen previously for high sucrose diets (~40% of daily caloric intake within 10 min) plus excess weight gain and adiposity, but absent increased anxiety-like behavior during elevated plus-maze or defensive withdrawal tests after diet withdrawal. Binge-like intake was unaffected by pretreatment with the corticotropin-releasing factor type 1 (CRF(1)) receptor antagonist R121919, and corticosterone responses to restraint stress did not differ between sweet-fat binge rats and chow-fed controls. In contrast, pretreatment with the cannabinoid type 1 (CB(1)) receptor antagonist SR147778 dose-dependently reduced binge-like intake, albeit less effectively than in ad lib chow or sweet fat controls. A priming dose of the sweet fat diet did not precipitate increased anxiety-like behavior, but rather increased plus-maze locomotor activity. The results suggest that CB(1)-dependent positive reinforcement rather than CRF(1)-dependent negative reinforcement mechanisms predominantly maintain excessive intake in this limited access model of sweet-fat diet binges.

Topics: Animals; Anxiety; Bulimia; Cannabinoid Receptor Antagonists; Corticosterone; Dietary Fats; Dietary Sucrose; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Maze Learning; Motor Activity; Piperidines; Pyrazoles; Pyrimidines; Rats; Rats, Wistar; Receptors, Corticotropin-Releasing Hormone

The purpose of this study was to determine if a cannabinoid CB(1) receptor antagonist would selectively decrease consumption of highly palatable food in non-human primates. The CB(1) receptor antagonist SR141716 (rimonabant; 0.12-1.0 mg/kg, i.m.) and the stimulant anorectic drug d-amphetamine (0.12-1.0 mg/kg, i.m.) were administered to non-food deprived baboons for the purpose of measuring the effect of each drug on consumption of the normal diet, and a large single meal of a high-carbohydrate candy. Four male and four female baboons had access to food 24 h each day, but they had to complete a two phase operant procedure in order to eat. Responding on one lever during a 30-min appetitive phase was required before animals could start a consumption phase, where responding on another lever led to food delivery, i.e., a meal. Three days a week baboons received a jelly sugar-coated candy (Skittles) during the first meal and then pellets were available in subsequent meals. All baboons ate as many individual candies in one meal as they did pellets throughout the entire day. Acute d-amphetamine and, to a lesser extent, SR141716 decreased both candy intake in a single meal and pellet intake in a single meal and over 24 h. d-Amphetamine, but not SR141716, increased latency to the candy meal and the first pellet meal indicating that the two drugs differentially altered feeding topography. Although males ate more food pellets than females, few other sex differences were observed. Thus, although effective in decreasing food intake, there was no evidence of a specific effect of CB(1) receptor antagonism on consumption of a large meal or a palatable food.

Topics: Animals; Appetite Depressants; Bulimia; Central Nervous System Stimulants; Dextroamphetamine; Eating; Female; Food Preferences; Humans; Male; Models, Animal; Papio cynocephalus; Piperidines; Pyrazoles; Receptor, Cannabinoid, CB1; Rimonabant; Satiety Response; Sex Characteristics

Bulimia nervosa has been associated with alterations in central serotonergic (5-HT) function. This study investigated iodine-labeled 4-amino-N-[1-[3-(4-fluorophenoxy) propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide ((123)I-5-I-R91150) binding to the 5-HT(2A) receptor in the brain by using single photon emission computed tomography in acutely ill bulimia nervosa patients.. Cortical (123)I-5-I-R91150 binding in 10 normal-weight patients with bulimia nervosa, purging type, was compared with that of 11 healthy volunteers.. The 5-HT(2A) binding index of the bulimia nervosa patients, with and without correction for age, was not significantly different from that of the comparison group.. As a group, acutely ill bulimia nervosa patients cannot be discriminated from healthy subjects on the basis of cortical (123)I-5-I-R91150 binding to the 5-HT(2A) receptor.

Topics: Acute Disease; Adolescent; Adult; Body Mass Index; Body Weight; Bulimia; Cerebral Cortex; Female; Humans; Iodine Radioisotopes; Male; Piperidines; Protein Binding; Receptor, Serotonin, 5-HT2A; Tomography, Emission-Computed, Single-Photon

Whether or not peptide YY (PYY)-induced hyperphagia is modified by the histaminergic system in the brain is not yet known.. We investigated the effect on feeding of intracerebroventricular (ICV) administration of a specific histamine H3 receptor antagonist prior to ICV administration of PYY in rats.. PYY (1, 3, and 10 micrograms/10 microL) strongly induced feeding behavior in a dose-dependent manner in sated rats. The 4-hour food intake induced by 3 micrograms/10 microL of PYY was equal to that induced by a 16-hour fast. The ICV administration of thioperamide (40.8, 122.4, and 408.5 micrograms/10 microL) did not suppress the 4-hour food intake induced by 16-hour fasting; however, thioperamide produced dose-dependent and strong inhibition of hyperphagia induced by a 3-microgram dose of PYY.. These results suggest that the effect of PYY on appetite is different than that induced by fasting and may involve a histaminergic mechanism.

Topics: Analysis of Variance; Animals; Appetite Regulation; Bulimia; Disease Models, Animal; Dose-Response Relationship, Drug; Drinking; Eating; Fasting; Histamine Antagonists; Hyperphagia; Injections, Intraventricular; Male; Peptide YY; Piperidines; Rats; Rats, Wistar; Receptors, Histamine H3; Satiation; Time Factors

Dysphonia associated with bulimia has been described in the literature associated with vocal fold edema and polypoid changes. Laryngopharyngeat reflux (LPR) has been documented to cause reflux vocal fold pathology including edema and polypoid changes. We studied eight singers with bulimia and documented vocal fold pathology, including edema, posterior commissure hypertrophy, ventricular obliteration, and telangiectasia. Reflux was demonstrated in all eight. The results of this study showed that LPR may be a contributing factor to vocal disorders in singers with bulimia.

Topics: Adult; Anti-Ulcer Agents; Bulimia; Cisapride; Female; Gastroesophageal Reflux; Humans; Omeprazole; Piperidines; Voice Disorders

Women with bulimia nervosa undergoing treatment with the reversible monoamine oxidase type A inhibitor, brofaromine, were rated for mood and eating behaviour and their plasma and urine were assessed for phenylacetic acid (unconjugated and total) and unconjugated phenylethylamine prior to and after four weeks of drug treatment. Changes in plasma unconjugated phenylacetic acid concentrations were significantly and negatively correlated with the corresponding changes in Hamilton Depression scores but not with eating behavior measures. There were no significant correlations between changes in phenylethylamine levels and changes in rating scores. Patients diagnosed as suffering concurrently from severe depression (Hamilton Depression score of 17 or higher) had lower plasma and urinary phenylacetic acid levels than did those whose depression was not severe (Hamilton score less than 17). Phenylethylamine concentrations were not different between the severely and mildly depressed subgroups. The results confirm earlier studies on the relationship between phenylacetic acid and depression while showing that a similar relationship does not pertain to phenylacetic acid and eating behavior in bulimia nervosa.

Topics: Adult; Bulimia; Depressive Disorder; Female; Humans; Monoamine Oxidase Inhibitors; Phenylacetates; Piperidines; Placebos; Psychiatric Status Rating Scales; Severity of Illness Index; Single-Blind Method