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

Suplicy, Henrique Lacerda; Boguszewski, César Luiz; Santos, Cid Aimbiré de Moraes; Figueiredo, Maria do Desterro de; Cunha, D R; Radominski, Rosana Bento

doi:10.1038/ijo.2013.225

Cited by 42 publications

(44 citation statements)

References 37 publications

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“…Previous studies in humans revealed that at appropriate concentrations, DEP, PHEN, and BUP produce weight loss (Hendricks et al 2009) with the order DEP Ն PHEN Ͼ BUP (Cercato et al 2009;Suplicy et al 2014). In the present study, using rats, we found that DEP20 was slightly more potent than PHEN20 with regard to weight loss (Fig.…”

Section: Comparison Of the Appetite Suppressantssupporting

confidence: 64%

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

Kalyanasundar

Pérez

Luna

et al. 2015

Journal of Neurophysiology

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R. 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. J Neurophysiol 114: 585-607, 2015. First published May 13, 2015 doi:10.1152/jn.00012.2015.-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 shortterm 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.

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Section: Comparison Of the Appetite Suppressantssupporting

confidence: 64%

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

Kalyanasundar

Pérez

Luna

et al. 2015

Journal of Neurophysiology

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“…Modern treatment regimens for obesity combine diet, exercise, behavioral psychotherapy, and in severe cases, gastrointestinal surgery to reduce craving and resist food consumption [von Deneen and Liu, 2011]. The available pharmacological treatments for obesity are relatively ineffective and expansive, and have their drawbacks [Suplicy et al, 2014]. The available pharmacological treatments for obesity are relatively ineffective and expansive, and have their drawbacks [Suplicy et al, 2014].…”

Section: Introductionmentioning

confidence: 99%

Oxytocin enhances cognitive control of food craving in women

Striepens

Schroter

Stoffel‐Wagner

et al. 2016

Human Brain Mapping

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In developed countries, obesity has become an epidemic resulting in enormous health care costs for society and serious medical complications for individuals. The homeostatic regulation of food intake is critically dependent on top-down control of reward-driven food craving. There is accumulating evidence from animal studies that the neuropeptide oxytocin (OXT) is involved in regulating hunger states and eating behavior, but whether OXT also contributes to cognitive control of food craving in humans is still unclear. We conducted a counter-balanced, double-blind, within-subject, pharmacological magnetic resonance imaging experiment involving 31 healthy women who received 24 IU of intranasal OXT or placebo and were scanned twice while they were exposed to pictures of palatable food. The participants were instructed either to imagine the immediate consumption or to cognitively control the urge to eat the food. Our results show a trend that OXT specifically reduced food craving in the cognitive control condition. On the neural level, these findings were paralleled by an increase of activity in the middle and superior frontal gyrus, precuneus, and cingulate cortex under OXT. Interestingly, the behavioral OXT effect correlated with the OXT-induced changes in the prefrontal cortex and precuneus. Collectively, the present study provides first evidence that OXT plays a key role in the cognitive regulation of food craving in women by strengthening activity in a broad neurocircuitry implicated in top-down control and self-referential processing. Hum Brain Mapp 37:4276-4285, 2016. © 2016 Wiley Periodicals, Inc.

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“…Several antiobesity drugs, including diethylpropion, fenproporex, mazindol, fluoxetine, and sibutramine, have been developed [14], but there is little evidence for effective and safe treatments. …”

Section: Introductionmentioning

confidence: 99%

Nasal Oxytocin Administration Reduces Food Intake without Affecting Locomotor Activity and Glycemia with c-Fos Induction in Limited Brain Areas

et al. 2015

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Recent studies have considered oxytocin (Oxt) as a possible medicine to treat obesity and hyperphagia. To find the effective and safe route for Oxt treatment, we compared the effects of its nasal and intraperitoneal (IP) administration on food intake, locomotor activity, and glucose tolerance in mice. Nasal Oxt administration decreased food intake without altering locomotor activity and increased the number of c-Fos-immunoreactive (ir) neurons in the paraventricular nucleus (PVN) of the hypothalamus, the area postrema (AP), and the dorsal motor nucleus of vagus (DMNV) of the medulla. IP Oxt administration decreased food intake and locomotor activity and increased the number of c-Fos-ir neurons not only in the PVN, AP, and DMNV but also in the nucleus of solitary tract of the medulla and in the arcuate nucleus of the hypothalamus. In IP glucose tolerance tests, IP Oxt injection attenuated the rise of blood glucose, whereas neither nasal nor intracerebroventricular Oxt affected blood glucose. In isolated islets, Oxt administration potentiated glucose-induced insulin secretion. These results indicate that both nasal and IP Oxt injections reduce food intake to a similar extent and increase the number of c-Fos-ir neurons in common brain regions. IP Oxt administration, in addition, activates broader brain regions, reduces locomotor activity, and affects glucose tolerance possibly by promoting insulin secretion from pancreatic islets. In comparison with IP administration, the nasal route of Oxt administration could exert a similar anorexigenic effect with a lesser effect on peripheral organs.

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

Abstract: 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.

Cited by 42 publications

References 37 publications

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

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

Oxytocin enhances cognitive control of food craving in women

Nasal Oxytocin Administration Reduces Food Intake without Affecting Locomotor Activity and Glycemia with c-Fos Induction in Limited Brain Areas

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