Locomotion is the major determinant of sibutramine-induced increase in energy expenditure

Golozoubova, Valeria; STRAUSS, FRANK G.; Malmlöf, Kjell

doi:10.1016/j.pbb.2006.03.014

Cited by 26 publications

(27 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This notion is supported by the observation that stimulation of monoaminergic neurotransmission also impacts the metabolic rate by increasing energy expenditure, either directly by increasing thermogenesis through activation of peripheral b 3 adrenoceptors in brown adipose tissue, or indirectly by increasing central DA receptor-dependent motor activity. These combined effects are reported for a number of MRIs, including the dual NE/5-HT and NE/DA reuptake inhibitors, sibutramine, and buproprion, respectively (Connoley et al, 1999;Liu et al, 2004;Golozoubova et al, 2006;Billes and Cowley, 2008). Although it should be noted that no tolerance to the appetite suppressing effect of tesofensine is observed in clinical settings (Astrup et al, 2008a), one possibility that warrants further investigation is whether sustained weight loss with tesofensine may involve increased energy expenditure.…”

Section: Discussionmentioning

confidence: 95%

Tesofensine, a Novel Triple Monoamine Reuptake Inhibitor, Induces Appetite Suppression by Indirect Stimulation of α1 Adrenoceptor and Dopamine D1 Receptor Pathways in the Diet-Induced Obese Rat

Axel

Mikkelsen

Hansen

2010

Neuropsychopharmacol

View full text Add to dashboard Cite

Tesofensine is a novel monoamine reuptake inhibitor that inhibits both norepinephrine, 5-HT, and dopamine (DA) reuptake function. Tesofensine is currently in clinical development for the treatment of obesity, however, the pharmacological basis for its strong effect in obesity management is not clarified. Using a rat model of diet-induced obesity (DIO), we characterized the pharmacological mechanisms underlying the appetite suppressive effect of tesofensine. DIO rats treated with tesofensine (2.0 mg/kg, s.c.) for 16 days showed significantly lower body weights than vehicle-treated DIO rats, being reflected by a marked hypophagic response. Using an automatized food intake monitoring system during a 12 h nocturnal test period, tesofensine-induced hypophagia was investigated further by studying the acute interaction of a variety of monoamine receptor antagonists with tesofensine-induced hypophagia in the DIO rat. Tesofensine (0.5-3.0 mg/kg, s.c.) induced a dose-dependent and marked decline in food intake with an ED 50 of 1.3 mg/kg. The hypophagic response of tesofensine (1.5 mg/kg, s.c.) was almost completely reversed by co-administration of prazosin (1.0 mg/kg, a 1 adrenoceptor antagonist) and partially antagonized by co-administration of SCH23390 (0.03 mg/kg, DA D 1 receptor antagonist). In contrast, tesofensine-induced hypophagia was not affected by RX821002 (0.3 mg/kg, a 2 adrenoceptor antagonist), haloperidol (0.03 mg/kg, D 2 receptor antagonist), NGB2904 (0.1 mg/kg, D 3 receptor antagonist), or ritanserin (0.03 mg/kg, 5-HT 2A/C receptor antagonist). Hence, the mechanism underlying the suppression of feeding by tesofensine in the obese rat is dependent on the drug's ability to indirectly stimulate a 1 adrenoceptor and DA D 1 receptor function.

show abstract

Section: Discussionmentioning

confidence: 95%

Tesofensine, a Novel Triple Monoamine Reuptake Inhibitor, Induces Appetite Suppression by Indirect Stimulation of α1 Adrenoceptor and Dopamine D1 Receptor Pathways in the Diet-Induced Obese Rat

Axel

Mikkelsen

Hansen

2010

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…DA reuptake inhibition also accounts for increased locomotion by other mixed monoamine reuptake inhibitors including psychostimulants and the weight loss drug sibutramine (Missale et al, 1998;Izenwasser et al, 1999;Golozoubova et al, 2006;Mitchell et al, 2006). Thus, the finding that BUP increases locomotor activity is widely supported.…”

Section: Discussionmentioning

confidence: 97%

“…Pharmacological and genetic studies support this assertion. Elevated activity and temperature have already been demonstrated to account for increased energy expenditure caused by treatment with the weight loss drug sibutramine (Liu et al, 2002;Golozoubova et al, 2006). In mice on a highfat diet, elevated activity and temperature prevent weight gain.…”

Section: Discussionmentioning

confidence: 99%

Catecholamine Reuptake Inhibition Causes Weight Loss by Increasing Locomotor Activity and Thermogenesis

Billes

Cowley

2007

Neuropsychopharmacol

View full text Add to dashboard Cite

Bupropion (BUP) is a dopamine (DA) and norepinephrine (NE) reuptake inhibitor that causes mild weight loss in obese adults. Subchronic (7 day) coadministration of selective DA and NE reuptake inhibitors also causes weight loss in mice. Because weight loss was not associated with decreased caloric intake, subchronic BUP might cause weight loss through increased energy expenditure. Acute studies demonstrate that BUP or DA + NE reuptake inhibitors cause transient hypophagia and increased locomotion; though the effects on temperature are inconsistent. Because subchronic DA + NE reuptake inhibition does not affect appetite, there is clearly a difference between the acute and subchronic effects of DA + NE reuptake inhibitors; however the effects of chronic (or subchronic) BUP on energy balance have never been directly studied in an animal model. Therefore, the acute and subchronic effects of BUP or selective DA and NE reuptake inhibitors on food intake, body weight, locomotor activity, and interscapular temperature were determined in mice. Generally, selective inhibition of DA reuptake (by GBR12783) increased activity while selective inhibition of NE reuptake (by nisoxetine, NIS) decreased activity and temperature. BUP increased activity and temperature but subchronic BUP did not significantly reduce body weight due to a compensatory increase in food intake. Subchronic DA + NE reuptake inhibitor coadministration mimicked the effect of BUP on activity and temperature, but caused weight loss because daily food intake was not increased. The results of this study suggest that the mild weight loss effect of BUP in humans may be due to increased locomotion or heat production. More importantly, inhibition of DA + NE reuptake (with GBR + NIS) increased energy expenditure without a compensatory increase in food intake, supporting a role for novel combination catecholamine reuptake inhibitors in pharmacotherapy for obesity.

show abstract

“…Metergoline is a non selective 5-HT receptor antagonist and was used at doses effective in blocking the in vivo effects induced by 5-HT receptor agonists in rats (Golozoubova et al, 2006;Mockler et al, 1983;Stachowicz et al, 2007). Rats were (Fletcher et al, 1996) or GR 127935 (a 5-HT 1B/D receptor antagonist) (Skingle et al, 1996).…”

Section: Dose Related Effects Of Metergoline On the Antidepressant-limentioning

confidence: 99%

A role for serotonin in the antidepressant activity of NG-Nitro-L-arginine, in the rat forced swimming test

Gigliucci

Buckley

Nunan

et al. 2010

Pharmacology Biochemistry and Behavior

View full text Add to dashboard Cite

show abstract

Locomotion is the major determinant of sibutramine-induced increase in energy expenditure

Cited by 26 publications

References 27 publications

Tesofensine, a Novel Triple Monoamine Reuptake Inhibitor, Induces Appetite Suppression by Indirect Stimulation of α1 Adrenoceptor and Dopamine D1 Receptor Pathways in the Diet-Induced Obese Rat

Tesofensine, a Novel Triple Monoamine Reuptake Inhibitor, Induces Appetite Suppression by Indirect Stimulation of α1 Adrenoceptor and Dopamine D1 Receptor Pathways in the Diet-Induced Obese Rat

Catecholamine Reuptake Inhibition Causes Weight Loss by Increasing Locomotor Activity and Thermogenesis

A role for serotonin in the antidepressant activity of NG-Nitro-L-arginine, in the rat forced swimming test

Contact Info

Product

Resources

About