Diethylpropion Research Articles

S2978 A Case of Severe Ischemic Duodenitis Secondary to Weight Loss Medication

Introduction: Diethylpropion hydrochloride (Diethylpropion HCL) is a sympathomimetic similar to amphetamine. It acts centrally to suppress appetite. We report a case of severe ischemic duodenitis in a male patient three weeks after starting diethylpropion HCL. Case Description/Methods: A 42-year-old white male with a medical history of obesity, hypertension and nonalcoholic fatty liver disease presented to the hospital due to four hours of epigastric pain and intractable nausea and vomiting. One week prior to presentation, he started taking diethylpropion HCL75 mg daily for weight loss. The physical exam was normal except for moderate epigastric tenderness. There was no guarding or rebound. Bowel sounds were normal. Murphy sign was negative. The laboratory tests white cell count 12.7x 109/L, hemoglobin 18.2 mg/dl and hematocrit 52.2%. Troponin, liver enzymes, total bilirubin and pancreatic enzymes were normal. An electrocardiography revealed no acute ischemic changes. Computed tomography of the abdomen revealed thickening of the gastric walls. An esophagogastroduodenoscopy (EGD), performed within 24 hours of hospitalization, demonstrated mild diffuse erythema in the antrum suggestive of mild gastritis. The duodenal bulb was normal. Distal to the ampulla, there is severe patchy erythema with ulcerations and edema suggestive of severe duodenitis (figure1, B). The biopsy revealed an ulcerated duodenal mucosa and villous atrophy. There was hemorrhage along with hyalinization of the lamina propria and atrophy of the deep aspects of the glands (figure1, A). These features suggest ischemic-type mucosal injury. The etiology was deemed to be secondary to phentermine. The patient was treated with intravenous fluids and was discharged home after 2 days of inpatient care. Four weeks later, he was asymptomatic, did not resume diethylpropion HCL and EGD revealed resolution of the ischemic duodenitis. Discussion: This case describes an association between the use of diethylpropion HCL and ischemic duodenitis. There are no published reports about the association between diethylpropion HCL and ischemic duodenitis. However, there are two case reports linking the use of phentermine, to ischemic colitis. As the use of weight loss medications has been increasing over the last few years, clinicians should be aware of potential ischemic duodenitis when prescribed.Figure 1.: Biopsy shows ulcerated duodenal, villous atrophy, hemorrhage and hyalinization of the lamina propria (A), severe patchy erythema with ulcerations and edema in the second part of the duodenum (B).

Meta-analysis and Approach of the Real Impact of Anorexigenic Drugs in the Obesity in Humans: The Last Five Years of the Randomized Studies.

Obesity shows a multifactorial disease and presents a serious public health problem, with an alarming epidemic character. According to NHANES (National Health and Nutrition Examination Survey) from 2015 to 2016, 39.6% of American adults and 18.5% of young people were obese and 7.7% of adults and 5.6% of young people had severe obesity. Brazil ranks fifth in the world ranking, with about 18 million people reaching up to 70 million overweight individuals. Despite shortterm weight loss with diet and exercise, weight regain continues to be a concern. Anti-obesity drugs, such as Sibutramine (SIB), Phentermine (PHEN), Fenproporex (FEN), Mazindol (MAZ), Amfepramone (AMFE) and Orlistat (ORL) may play a role in weight reduction in patients whose condition is refractory to non- and maintenance of weight loss. A systematic review followed by meta-analysis of randomized clinical trials over the past five years to explore the efficacy and safety of anorexigenic drugs for weight reduction and consequent treatment of obesity. The search strategy in MEDLINE / Pubmed, Web of Science, ScienceDirect Journals (Elsevier), Scopus (Elsevier), OneFile (Gale) is as follows : - search for mesh terms (Sibutramine, Phentermine, Fenproporex, Mazindol, Amfepramone , Orlistat, Weight loss, Safety), and the use of booleans "and" between mesh terms and "or" among historical findings. It was observed that in the last five years of randomized studies no significant general complications were found, with only 5.7%. The mean overall weight loss was 6.18 (± 2.8) kg in the mean time of 12 months. The overall success rate among these drugs was 80.18%. The p-value values did not present a significant statistical difference, being p <0.05 within each drug group analyzed, for both weight and success rates. The scientific findings of randomized studies on the use of anorexigenic drugs to treat obesity have shown safety and efficiency in the last five years, with a reasonable weight loss and no significant complications.

Short post-weaning social isolation induces long-term changes in the dopaminergic system and increases susceptibility to psychostimulants in female rats

Childhood and adolescence are sensitive periods of development, marked by high brain maturation and plasticity. Exposure to early life stress, such as social isolation, is able to prompt changes in sensitive brain circuitries, essentially in the mesolimbic dopaminergic system and increase the risk for addictive behaviors later in life. Post-weaning social isolation can stimulate the consumption of rewarding substances, like drugs of abuse and palatable foods. However, most studies analyze long periods of social isolation and very little is known about the effects of a brief social isolation in a sensitive period of development and its association with palatable food on the reward system sensitization. Furthermore, females are more susceptible to the reinforcing effect of drugs than males. Therefore, the aim of this study was to analyze the effects of a short post-weaning social isolation combined with a free access to a chronic high sugar diet (HSD) on the dopaminergic system, oxidative status and behavioral response to an amphetamine-like drug in adulthood. We used female Wistar rats that were socially isolated from post-natal days (PD) 21 to 35 and received free access to a HSD until PD 60. On PD 65, animals were submitted to a challenge with diethylpropion (DEP), an amphetamine-like drug and different responses were analyzed: locomotor activity, immmunocontent of dopamine related proteins, and the oxidative status in the striatum, before and after the DEP challenge. We showed that a short post-weaning social isolation (SI) increased the locomotor response to DEP, when compared with previous saline administration. Social isolation also increased dopamine transporter, tyrosine hydroxylase, and decreased dopamine D2 receptor immunocontent. Additionally, SI increased the overall oxidative status parameters after the challenge with DEP. Interestingly, the exposure to a HSD prevented the SI effects on locomotor response, but did not interfere in the dopaminergic parameters evaluated, despite having modified some oxidative parameters. This study showed for the first time that a short post-weaning social isolation was able to induce long-term changes in the striatal dopaminergic system and increased the response to psychostimulants. These results emphasize the importance of stressful experiences during a short period of development on programming susceptibility to psychostimulants later in life.

The efficacy of the appetite suppressant, diethylpropion, is dependent on both when it is given (day vs. night) and under conditions of high fat dietary restriction

Obesity is a public health problem caused by excessive consumption of high caloric diets and/or lack of physical activity. Although treatments for obesity include low caloric diets and exercise programs, these activities frequently are supplemented with appetite suppressants. For the short-term treatment of weight loss, diethylpropion (DEP) is a commonly used appetite suppressant. However, little is known with regard to how to improve its weight loss efficacy. We therefore evaluated, in rats, two administration protocols where the animals received daily injections of DEP. First, when these nocturnal animals were normally active (at night) and when they were normally inactive (daytime), and second, with or without high fat dietary restriction (HFDR). We observed that DEP induced a greater weight-loss administered when the animals were in their active phase than in their inactive phase. Moreover, DEP's administration during the inactive phase (and to a lesser degree in the active phase) promotes the consumption of food during normal sleeping time. In addition, we found that DEP-induced weight loss under ad libitum access to a HF diet, but its efficacy significantly improved under conditions of HFDR. In summary, the efficacy of DEP, and presumably other like appetite suppressants, is enhanced by carefully controlling the time it is administered and under dietary restriction of HF diets.

Differential pulse voltammetric determination of amfepramone in pharmaceutical formulations and serum samples using glassy carbon electrode

The electrochemical reduction of amfepramone (AFPN) was investigated systematically by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). A simple DPV technique was proposed for the direct quantitative determination of amfepramone (AFPN) in pharmaceutical formulations and serum samples for the first time. The reduction potential was -1.0V with glassy carbon electrode in phosphate buffer as supporting electrolyte. The dependence of the intensities of currents and potentials on pH, concentration, scan rate, deposition time, and nature of the supporting electrolyte was investigated. In the present investigation, the achieved limit of detection (LOD) was 3.2x10 -8 M and a limit of quantification (LOQ) was 6.2x10 -9 M respectively. Excipients did not interfere with the determination of amfepramone (AFPN) in pharmaceutical formulations and serum samples. Precision and accuracy of the developed method were checked by recovery studies in pharmaceutical formulations and blood samples.

D1 and D2 antagonists reverse the effects of appetite suppressants on weight loss, food intake, locomotion, and rebalance spiking inhibition in the rat NAc shell.

Obesity is a worldwide health problem that has reached epidemic proportions. To ameliorate this problem, one approach is the use of appetite suppressants. These compounds are frequently amphetamine congeners such as diethylpropion (DEP), phentermine (PHEN), and bupropion (BUP), whose effects are mediated through serotonin, norepinephrine, and dopaminergic pathways. The nucleus accumbens (NAc) shell receives dopaminergic inputs and is involved in feeding and motor activity. However, little is known about how appetite suppressants modulate its activity. Therefore, we characterized behavioral and neuronal NAc shell responses to short-term treatments of DEP, PHEN, and BUP. These compounds caused a transient decrease in weight and food intake while increasing locomotion, stereotypy, and insomnia. They evoked a large inhibitory imbalance in NAc shell spiking activity that correlated with the onset of locomotion and stereotypy. Analysis of the local field potentials (LFPs) showed that all three drugs modulated beta, theta, and delta oscillations. These oscillations do not reflect an aversive-malaise brain state, as ascertained from taste aversion experiments, but tracked both the initial decrease in weight and food intake and the subsequent tolerance to these drugs. Importantly, the appetite suppressant-induced weight loss and locomotion were markedly reduced by intragastric (and intra-NAc shell) infusions of dopamine antagonists SCH-23390 (D1 receptor) or raclopride (D2 receptor). Furthermore, both antagonists attenuated appetite suppressant-induced LFP oscillations and partially restored the imbalance in NAc shell activity. These data reveal that appetite suppressant-induced behavioral and neuronal activity recorded in the NAc shell depend, to various extents, on dopaminergic activation and thus point to an important role for D1/D2-like receptors (in the NAc shell) in the mechanism of action for these anorexic compounds.

Simultaneous analysis of amphetamine-type stimulants in plasma by solid-phase microextraction and gas chromatography-mass spectrometry.

Brazil is considered one of the countries with the highest number of amphetamine-type stimulant (ATS) users worldwide, mainly diethylpropion (DIE) and fenproporex (FEN). The use of ATS is mostly linked to diverted prescription stimulants and this misuse is widely associated with (ab)use by drivers. A validated method was developed for the simultaneous analysis of amphetamine (AMP), DIE and FEN in plasma samples employing direct immersion-solid-phase microextraction, and gas chromatographic/mass spectrometric analysis. Trichloroacetic acid 10% was used for plasma deproteinization. In situ derivatization with propylchloroformate was employed. The linear range of the method covered from 5.0 to 100 ng/mL. The detection limits were 1.0 (AMP), 1.5 (DIE) and 2.0 ng/mL (FEN). The accuracy assessment of the control samples was within 85.58-108.33% of the target plasma concentrations. Recoveries ranged from 46.35 to 84.46% and precision was <15% of the value of relative standard deviation. This method is appropriate for screening and confirmation in plasma forensic toxicology analyses of these basic drugs.

A comparative study of five centrally acting drugs on the pharmacological treatment of obesity

No long-term studies have compared centrally acting drugs for treating obesity. To compare the efficacy and safety of diethylpropion (DEP), fenproporex (FEN), mazindol (MZD), fluoxetine (FXT) and sibutramine (SIB) in promoting weight loss. A prospective, randomized, placebo (PCB)-controlled study conducted at a single academic institution. A total of 174 obese premenopausal women. Participants randomly received DEP 75 mg (n=28), FEN 25 mg (n=29), MZD 2 mg (n=29), SIB 15 mg (n=30), FXT 20 mg (n=29) or PCB (n=29) daily over 52 weeks. Diet and physical activity were encouraged. The primary endpoints were changes in body weight and the proportion of women who achieved at least 5% weight loss by week 52 in the intent-to-treat population. Other measurements included anthropometry, safety, metabolic and cardiovascular parameters. Weight loss was greater than PCB (-3.1±4.3 kg) with DEP (-10.0±6.4 kg; P<0.001), SIB (-9.5±5.9 kg; P<0.001), FEN (-7.8±6.9 kg; P<0.01) and MZD (-7.4±4.9 kg; P<0.01) but not with FXT (-2.5±4.1 kg). Ten (33.3%) women lost⩾5% of their initial weight with PCB, compared with 20 (71.4%; P<0.001) with DEP, 20 (69%; P<0.02) with FEN, 21 (72.4%; P<0.01) with MZD, 22 (73.3%; P<0.001) with SIB and 10 (35.5%) with FXT. Each medically treated group experienced more adverse events compared with PCB (P<0.001). Compared with PCB, constipation was more prevalent with DEP, SIB and MZD (P<0.01); anxiety was more prevalent with DEP (P=0.01); and irritability occurred more frequently with DEP and FEN (P=0.02). Significant improvements in the depression and anxiety scores, binge-eating episodes and quality of life correlated with weight loss. The centrally acting drugs DEP, FEN, MZD and SIB were more effective than PCB in promoting weight loss in obese premenopausal women, with a satisfactory benefit-risk profile.

A GC–EI-MS-MS Method for Simultaneous Determination of Seven Adulterants in Slimming Functional Foods

A gas chromatography-electron impact-tandem mass spectrometric method was established for the simultaneous determination of seven adulterants, including fenfluramine (FEN), norpseudoephedrine (NPE), pseudoephedrine (PSE), ephedrine (EPH), amfepramone (AMF), sibutramine (SIB) and strychnine (STR) in slimming functional foods. The target chemicals were extracted with 2% formic acid solution and then cleaned-up with solid-phase extraction using a strong cation exchange cartridge from tablet, liquid, mixed plant powder and capsule formulations. Chromatographic separation was accomplished on a VF-5MS column within 23 min. Leucomalachite green was employed as an internal standard. The recoveries of seven target chemicals in two formulations ranged from 80.1 to 106%. Limits of detection of the method were from 7.5 to 375 µg/kg with relative standard deviations of 1.6 to 13.9%. The linearity of the method ranged from 90 to 1500 ng/mL for NPE, 150 to 1500 ng/mL for STR, 10 to 500 ng/mL for AMF, 5.0 to 500 ng/mL for PSE and EPH and 3.0 to 500 ng/mL for FEN and SIB. This method was applied to the determination of six brands of slimming functional foods. SIB was detected in five of the samples with the contents in the range of 10.3 - 8.55 × 10(5) μg/kg.

Determination of amphetamine-type stimulants in oral fluid by solid-phase microextraction and gas chromatography–mass spectrometry

A method for the simultaneous identification and quantification of amphetamine (AMP), methamphetamine (MET), fenproporex (FEN), diethylpropion (DIE) and methylphenidate (MPH) in oral fluid collected with Quantisal™ device has been developed and validated. Thereunto, in-matrix propylchloroformate derivatization followed by direct immersion solid-phase microextraction and gas chromatography–mass spectrometry were employed. Deuterium labeled AMP was used as internal standard for all the stimulants and analysis was performed using the selected ion monitoring mode. The detector response was linear for the studied drugs in the concentration range of 2–256 ng mL −1 (neat oral fluid), except for FEN, whereas the linear range was 4–256 ng mL −1. The detection limits were 0.5 ng mL −1 (MET), 1 ng mL −1 (MPH) and 2 ng mL −1 (DIE, AMP, FEN), respectively. Accuracy of quality control samples remained within 98.2–111.9% of the target concentrations, while precision has not exceeded 15% of the relative standard deviation. Recoveries with Quantisal™ device ranged from 77.2% to 112.1%. Also, the goodness-of-fit concerning the ordinary least squares model in the statistical inference of data has been tested through residual plotting and ANOVA. The validated method can be easily automated and then used for screening and confirmation of amphetamine-type stimulants in drivers’ oral fluid.

Neurochemical and behavioral effects elicited by bupropion and diethylpropion in rats

This study is an attempt to demonstrate whether bupropion (BP) and diethylpropion (DEP) exert their pharmacological actions by similar neurochemical mechanisms in the dorsal striatum. In this regard, the release of dopamine (DA), glutamate (Glu), and GABA, was determined in the rat dorsal striatum after acute (5 min) and chronic (15 consecutive days) treatments, and subsequently correlated with the locomotor activities produced by these drugs. The results from the acute experiments indicate that BP and DEP (40 mg/kg) increase locomotor activity, whereas chronic DEP treatment decreases locomotor activity by unspecific mechanisms. Acute BP treatment produces significant DA and Glu, but not GABA, releases. A lesser extent of DA release and tissue content of DA and its metabolites, and consequently less locomotor activity, was observed after chronic BP treatment. Acute DEP (5 mg/kg) was only able to slightly increase DA release and to decrease the tissue levels of DA, but no other markers, with practically nil locomotor activity, whereas chronic DEP produced even less neurotransmitter release. The observed difference between BP and DEP might be based on that although both drugs inhibit the DA and norepinephrine transporters, the BP-induced nicotinic receptor inhibition has yet to be demonstrated for DEP.

Nonsurgical Weight Loss for Extreme Obesity in Primary Care Settings

Effective primary care practice (PCP) treatments are needed for extreme obesity. The Louisiana Obese Subjects Study (LOSS) tested whether, with brief training, PCPs could effectively implement weight loss for individuals with a body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 40 to 60. The LOSS, a 2-year (July 5, 2005, through January 30, 2008) randomized, controlled, "pragmatic clinical trial" trained 7 PCPs and 1 research clinic in obesity management. Primary outcome measure was year-2 percentage change from baseline weight. Volunteers (597) were screened and randomized to intensive medical intervention (IMI) (n = 200) or usual care condition (UCC) (n = 190). The UCC group had instruction in an Internet weight management program. The IMI group recommendations included a 900-kcal liquid diet for 12 weeks or less, group behavioral counseling, structured diet, and choice of pharmacotherapy (sibutramine hydrochloride, orlistat, or diethylpropion hydrochloride) during months 3 to 7 and continued use of medications and maintenance strategies for months 8 to 24. The mean age of participants was 47 years; 83% were women, and 75% were white. Retention rates were 51% for the IMI group and 46% for the UCC group (P = .30). After 2 years, the results were as follows: (1) among 390 randomized participants, 31% in the IMI group achieved a 5% or more weight loss and 7% achieved a 20% weight loss or more, compared with 9% and 1% of those in the UCC group. (2) The mean +/- SEM baseline observation carried forward analysis showed a weight loss of -4.9% +/- 0.8% in IMI and -0.2 +/- 0.3% in UCC. (3) Last observation carried forward analysis showed a weight loss of -8.3% +/- 0.79% for IMI, whereas UCC was -0.0% +/- 0.4%. (4) A total of 101 IMI completers lost -9.7% +/- 1.3% (-12.7 +/- 1.7 kg), whereas 89 UCC completers lost -0.4% +/- 0.7% (-0.5 +/- 0.9 kg); (P < .001 for all group differences). Many metabolic parameters improved. Primary care practices can initiate effective medical management for extreme obesity; future efforts must target improving retention and weight loss maintenance. clinicaltrials.gov Identifier: NCT00115063.

Abuse liability and safety of oral lisdexamfetamine dimesylate in individuals with a history of stimulant abuse

Lisdexamfetamine dimesylate (LDX) is the first prodrug stimulant and is indicated for the treatment of attention-deficit/hyperactivity disorder. A single-centre, double-blind, randomised, placebo-controlled, 6-period crossover study evaluated the abuse potential of single oral doses of 50, 100 (equivalent to 40 mg d-amphetamine), and 150 mg LDX, 40 mg d-amphetamine and 200 mg diethylpropion in 36 individuals with a history of stimulant abuse. On the primary abuse liability measure, maximum change of the Drug Rating Questionnaire-Subject Liking Scale compared with placebo, d-amphetamine and diethylpropion showed significant differences of 4.5 and 4.0 units, respectively (P < 0.001 for both vs placebo). LDX, administered at 50, 100 and 150 mg, showed nonsignificant differences of 2.0 and 2.1 units, respectively, at the two lower doses but a significant (P < 0.001 vs placebo) difference of 6.1 units at the highest dose. Subjects significantly favoured d-amphetamine 40 mg versus LDX 100 mg (2.4 units difference; P < 0.05). There was no significant difference in liking scores between d-amphetamine 40 mg and LDX 150 mg. Drug Rating Questionnaire-Subject Feel-Drug-Effect score was significantly lower for 100 mg LDX than for 40 mg d-amphetamine. There were no statistically significant differences between LDX and diethylpropion hydrochloride, a Schedule IV amphetamine-like stimulant, on abuse-related liking scores. Cardiovascular responses of LDX and d-amphetamine were similar at equivalent doses. In conclusion, at an equivalent amount of amphetamine base taken orally, LDX 100 mg had attenuated responses on measures of abuse liability compared with immediate-release d-amphetamine 40 mg. Abuse-related liking scores of LDX at a dose corresponding to a 50% higher amphetamine base (LDX 150 mg) were similar to d-amphetamine 40 mg.

Diethylpropion produces psychostimulant and reward effects

Diethylpropion (DEP) is a stimulant drug widely used for weight control in Brazil and other American countries. However, its effects on behavior and addiction potential are not yet well known. Data suggest that sensitization resulting from pre-exposure to psychostimulants could be a possible risk factor in subsequent drug addiction. The purpose of this investigation was to verify whether pre-exposure to DEP would sensitize rats to the motor activating effect and to the rewarding value of DEP. Two experiments were conducted. In both experiments rats were pre-exposed to DEP (20 mg/kg) or vehicle for 7 consecutive days. The acute effect of DEP (0.0, 1.0, 2.5 or 5.0 mg/kg) on motor activity (Experiment 1) and induction of Conditioned Place Preference—CPP (Experiment 2) were then measured. Results from Experiment 1 showed that 2.5 and 5.0 mg/kg DEP increased motor activity. Sensitization of this motor effect was observed. In Experiment 2, the doses of 2.5 and 5.0 mg/kg DEP induced CPP, indicating their rewarding value. However, no sensitization effect was observed. The results suggest that DEP at low doses has psychostimulant and rewarding properties. It is recommended that more effort should be dedicated to elucidating DEP abuse potential.

Effects of diethylpropion treatment and withdrawal on aorta reactivity, endothelial factors and rat behavior

Diethylpropion (DEP) is an amphetamine-like compound used as a coadjutant in the treatment of obesity and which presents toxicological importance as a drug of abuse. This drug causes important behavioral and cardiovascular complications; however, the vascular and behavioral alterations during DEP treatment and withdrawal, have not been determined. We evaluated the effects of DEP treatment and withdrawal on the rat aorta reactivity to noradrenaline, focusing on the endothelium, and the rat behavior during DEP treatment and withdrawal. DEP treatment caused a hyporreactivity to noradrenaline in aorta, reversible after 2 days of withdrawal and abolished by both the endothelium removal and the presence of L-NAME, but not by the presence of indomethacin. Furthermore, DEP treatment increased the general activity of rats. Contrarily, DEP withdrawal caused a decrease in the locomotor activity and an increase in grooming behavior, on the 2nd and 7th days after the interruption of the treatment, respectively. DEP treatment also caused an adaptive vascular response to noradrenaline that seems to be dependent on the increase in the endothelial nitric oxide system activity, but independent of prostaglandins synthesis. The data evidenced chronological differences in the adaptive responses of the vascular and central nervous systems induced by DEP treatment. Finally, a reversion of the adaptive response to DEP was observed in the vascular system during withdrawal, whereas a neuroadaptive process was still present in the central nervous system post-DEP. These findings advance on the understanding of the vascular and behavioral pathophysiological processes involved in the therapeutic and abusive uses of DEP.

Neurotoxicity of Diethylpropion

The effects of diethylpropion (DEP), an amphetamine derivative and a well-known anorectic agent, on different neurochemical and behavioral markers of toxicity in rats were evaluated. Animals received a daily dose of DEP (5 mg/kg po) for 15 days, and all tests were performed 24 hours after the last DEP administration. As neurochemical markers, the brain regional levels of some amino acids, such as aspartate (Asp), glutamate (Glu), gamma-aminobutyric acid (GABA), and glutamine (Gln), as well as the brain regional rates of lipid peroxidation as a current index of oxidative stress were measured. As behavioral markers, the actions of DEP on both mercaptopropionic acid (MPA)-induced seizures and kainic acid (KA)-induced wet-dog body shakes were explored to investigate whether DEP induces behavioral sensitization to the effects of agents affecting the central activity of neuroactive amino acids. Treatment with DEP produced significant changes in the levels of Asp in the hypothalamus (Ht) and cortex (Cx); Glu in the Ht, Cx, midbrain (Mb), and striatum (S); and Gln in the Cx. The regional levels of GABA remain unchanged. Lipid peroxidation was increased in the hippocampus (Hc), Mb, and S. Also, latency to the first seizure induced by MPA (1.2 mmol/kg i.p.) and the total number of wet-dog body shakes induced by KA (10 mg/kg i.p.) were significantly affected by DEP treatment. These findings suggest that low doses of DEP may affect different neurochemical substrates, inducing changes in neuroactive amino acids along the brain regions, probably involving dopamine release. Consequently, behavioral changes could be the result of excitotoxic events related to excessive Glu or lack of an inhibitory process. Also, DEP is thought to involve free radical formation and oxidative stress as potential features of its regional pattern of neurotoxicity, as evidenced by lipid peroxidation.

Effects of amphetamine, dexfenfluramine, diazepam, and other pharmacological and dietary manipulations on food "seeking" and "taking" behavior in non-human primates.

Feeding consists of appetitive or foraging behavior followed by consummatory behavior. To determine if pharmacological manipulations can differentially affect appetitive and consummatory aspects of food intake, and to compare these results to those obtained using naturalistic dietary manipulations. Responding of baboons was studied using a schedule of reinforcement that simulated food "seeking" and food "taking." Responding during the seeking component was reinforced by stimuli paired with food, while responding during the taking component was reinforced with food. The effects of intramuscular amphetamine (AMPH), dexfenfluramine (DFEN), diethylpropion (DEP), phencyclidine (PCP), diazepam (DZP), as well as caloric prefeeding and acute food deprivation were determined. AMPH decreased food taking and increased food seeking, DEP decreased food taking without affecting food seeking, DFEN and PCP decreased both food taking and food seeking, while DZP increased both food taking and food seeking. Caloric prefeeding decreased food taking and increased food seeking, i.e., resembled AMPH, while acute deprivation increased both food taking and food seeking, i.e., resembled DZP. Manipulations that increase dopamine turnover, such as AMPH, increase food seeking, while decreasing food intake. In contrast, manipulations that increase serotonin turnover, such as DFEN, decrease both food seeking and food taking.

Long-term pharmacotherapy of obesity 2000: a review of efficacy and safety.

To clarify the efficacy of antiobesity drugs, this article reviews all long-term (> or =36 weeks), placebo-controlled trials of obesity pharmacotherapy published since 1960. Since fears of anorexiant-induced heart valve damage preclude many physicians and patients from even considering antiobesity drugs, this area is also reviewed in-depth. Electronic database and manual bibliography search was used to identify all relevant publications. While existing studies are too few and heterogeneous to warrant meta-analysis, their review does provide evidence highly relevant to the safety and efficacy of available anorexiants. Weight loss attributable to obesity pharmacotherapy (ie, in excess of placebo) in trials lasting 36 to 52 weeks was 8.1% or 7.9 kg for those receiving phentermine resin, 5.0 % or 4.3 kg for those receiving sibutramine hydrochloride, 3.4% or 3.4 kg for those receiving orlistat, and -1.5% or -1.5 kg for those receiving diethylpropion hydrochloride. Physiologic, pathologic, and epidemiological studies strongly support that anorexiant-induced valvulopathy is attributable to specific serotonergic properties of the fenfluramines that are not present with available weight loss drugs.

Efeitos da dietilpropiona, energia da dieta e sexo sobre o ganho de peso corporal, peso dos órgãos e deposição de tecidos em ratos

O objetivo deste trabalho foi avaliar a dietilpropiona (DEP), um derivado fenetilamínico utilizado como anorexígeno, e dietas de diferentes densidades calóricas, utilizando ratos de ambos os sexos. O experimento contou com 72 ratos Wistar distribuídos por sexo, bloqueados por peso inicial e alocados dois a dois em 36 gaiolas experimentais. As dietas e a água foram fornecidas ad libitum e atenderam a todas as exigências dos animais, sendo que a dieta de alta energia continha 3.700kcal de energia metabolizável (EM)/kg, a média 3.350kcal EM/kg e a baixa 3.000kcal EM/kg de ração. A droga foi administrada com uma dose diária de 20mg/kg, durante 36 dias, por via intraperitonial. A análise estatística considerou os efeitos da droga, energia da dieta, sexo, triplicata e a interação entre essas variáveis. Os resultados mostraram que houve interação entre dieta e droga (p&lt;0,0195) e que o uso da droga diminuiu o consumo alimentar apenas em dietas de baixa e média energias. A interação entre sexo e droga (p&lt;0,0253) mostrou que a droga reduziu o ganho de peso em ambos os sexos. Concluiu-se que a DEP reduziu o ganho de peso dos machos e das fêmeas, com redução de gordura depositada em ambos os sexos, sendo que as percentagens de deposição de gordura foram maiores nas fêmeas do que nos machos, os quais depositaram mais proteína. A DEP foi responsável pela redução no consumo de dietas de baixa e média energia metabolizável, não havendo efeito em dietas de alta energia.

Amfepramone ban lifted by UK MCA

Amfepramone ban lifted by UK MCA