Targeting the serotonin 2C receptor for the treatment of obesity and type 2 diabetes

Marston, Oliver; Heisler, Lora K.

doi:10.1038/npp.2008.169

Cited by 25 publications

(13 citation statements)

References 10 publications

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“…Drugs that increase serotonin availability in the synaptic cleft are used for treating obesity [21]. The SLC6A14 gene encodes an amino acid transporter that may affect tryptophan availability for serotonin synthesis.…”

Section: Discussionmentioning

confidence: 99%

SLC6A14 and 5-HTR2C polymorphisms are associated with food intake and nutritional status in children

Miranda

Vetter

Genro

et al. 2015

Clinical Biochemistry

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Section: Discussionmentioning

confidence: 99%

SLC6A14 and 5-HTR2C polymorphisms are associated with food intake and nutritional status in children

Miranda

Vetter

Genro

et al. 2015

Clinical Biochemistry

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“…In fact, therapeutic efficacy of fenfluramine (indirect 5-HT agonist) in obesity has previously been associated with its effect on 5-HT2C receptors (Miller 2005). In fact, this receptor subtype is considered a promising candidate for development of anti-obesity drugs, some of which are under development (Marston and Heisler 2009) and Belviq (Lorcaserin) relatively selective 5-HT2C agonist has been registered by Arena Pharmaceuticals (Brashier et al 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, anxiolytic effects of eltoprazine have been described (Sanchez 1997), but not intensively characterized and anorectic potential of substances acting at 5-HT2C receptors has also been shown (Marston and Heisler 2009), albeit not specifically for eltoprazine.…”

Section: Introductionmentioning

confidence: 99%

Further pharmacological characterization of eltoprazine: focus on its anxiolytic, anorexic, and adverse‑effect potential

Gravius¹,

Dekundy²,

Vanaga³

et al. 2017

Acta Neurobiologiae Experimentalis

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Eltoprazine, a drug that had previously been developed for aggression, has recently been investigated for L-DOPA-induced dyskinesia in animal models of Parkinson´s disease (PD) and in dyskinetic PD patients. Much less is known about effects of eltoprazine in other therapeutic indications. Indeed, the pharmacological profile of eltoprazine might suggest its effects on anxiety and food intake, but also adverse effect potential, which is the focus of the present study.Given for 2 weeks either as infusion or as twice-daily treatment, eltoprazine produced a decrease in food intake and body weight at doses leading to 200-500 nM plasma concentrations.In the elevated plus maze eltoprazine increased anxiety-like behavior. On the other hand, it induced a clear-cut anxiolytic effect in context fear conditioning test starting at ca. 0.3 mg/kg, and failed to produce any significant effect in fear potentiated startle test.Regarding adverse effects, eltoprazine was found to produce hypothermia starting from 1 mg/kg. At similar doses it also increased locomotion in the open field. However, eltoprazine failed to affect acquisition in context fear conditioning paradigm, which may indicate lack of its detrimental effect on learning at the doses tested (i.e., up to 5 mg/kg).In summary, effects of eltoprazine in different anxiety tests were equivocal while its effect on body weight seems robust and requires further investigation. It is to be determined whether these effects can be expected at the doses free of adverse effects.

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“…The role of serotonin in energy balance has been widely acknowledged. It has been characterized as a satiety signal, exerting its effects mainly through 5-HT 2C receptor activation (Giorgetti & Tecott, 2004 ;Hayashi et al 2005 ;Marston & Heisler, 2009 ;Martin et al 1998 ;Xu et al 2008 ;Zhou et al 2007). The anorexia induced by the activation of 5-HT 2C receptors occurs in hypothalamic nuclei (Xu et al 2008 ;Zhou et al 2007).…”

Section: Introductionmentioning

confidence: 97%

Oleamide administered into the nucleus accumbens shell regulates feeding behaviour via CB1 and 5-HT2C receptors

Soria-Gómez

Marquez-Diosdado

Montes-Rodrı́guez

et al. 2010

Int. J. Neuropsychopharm.

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The central nervous system control of food intake has been extensively studied, hence, several neurotransmitter systems regulating this function are now clearly identified, for example, the endocannabinoid and serotoninergic systems. The former stimulates feeding while the latter inhibits it. Oleamide (Ole) is a cannabimimetic molecule affecting both systems. In this work, we tested the orexigenic and anorectic potential of Ole when administered into the nucleus accumbens shell (NAcS), a brain region that has been related to the orexigenic effects of cannabinoids. Additionally, we tested if Ole administered into this nucleus affects the activity of the hypothalamic nuclei involved in feeding behaviour, just as other cannabinoids do. We found a hyperphagic effect of Ole that is mediated through CB1 activation. The combination of Ole and the CB1 antagonist, AM251, produced a hypophagia that was fully blocked by SB212084, a 5-HT2C receptor antagonist. We also show that blockade of 5-HT2C and 5-HT2A receptors in the NAcS stimulates food intake. Finally, the combination of Ole and AM251 activates hypothalamic nuclei, an effect also blocked by SB242084. In conclusion, we show, for the first time, that Ole administered into the NAcS has a dual effect on feeding behaviour, acting through cannabinoid and serotonin receptors. These effects probably result from a downstream interaction with the hypothalamus.

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Targeting the serotonin 2C receptor for the treatment of obesity and type 2 diabetes

Cited by 25 publications

References 10 publications

SLC6A14 and 5-HTR2C polymorphisms are associated with food intake and nutritional status in children

SLC6A14 and 5-HTR2C polymorphisms are associated with food intake and nutritional status in children

Further pharmacological characterization of eltoprazine: focus on its anxiolytic, anorexic, and adverse‑effect potential

Oleamide administered into the nucleus accumbens shell regulates feeding behaviour via CB1 and 5-HT2C receptors

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