Locomotor and peripheral effects of sibutramine modulated by 5-HT2 receptors.
Sibutramine has been described as an anti-obesity drug with the ability to inhibit serotonin (5-HT), noradrenaline, and dopamine re-uptake, but without affinity to histamine and muscarinic receptors. On the other hand, cyproheptadine antagonizes serotonin 5-HT(2A), 5-HT(2B), and 5-HT(2C), histamine H1, and muscarinic (M) receptors. There are many reports concerning the influence of sibutramine on central serotoninergic pathways. In this study, we suggest that peripheral pathways may also be involved in the serotoninergic effects of sibutramine. In vivo experiments were undertaken to investigate the serotoninergic effects of sibutramine on body mass, the glycogen concentration in the diaphragm of rats, and locomotor behaviour. Rats were submitted to oral treatment with sibutramine, cyproheptadine, or sibutramine applied in combination with cyproheptadine, for a period of 2 months to investigate the 5-HT2 effects of sibutramine on these parameters. As the results demonstrated, the lower increase in body mass and the increased glycogen levels in the diaphragm muscle of rats treated with sibutramine seem to be modulated by 5-HT2 receptors, since these effects were completely antagonized by cyproheptadine in the group treated with the 2 drugs co-applied. Furthermore, the behavioural results also suggest that mechanisms modulated by 5-HT2 receptors are involved in the increase of locomotion in the rats treated with sibutramine, since the effect did not occur in the rats treated with sibutramine co-applied with the 5-HT2 receptor antagonist, cyproheptadine. The results suggest that sibutramine modifies energy-related parameters such as body mass, diaphragm glycogen, and locomotor behaviour in rats via 5-HT2 serotoninergic pathways.
Frassetto
Silvana Soriano
SS
Universidade Luterana do Brasil, Curso de Farmácia e Biomedicina, Av. Farroupilha, 8001, Canoas, RS 92425-900, Brazil. vana@terra.com.br
Della Santa Rubio
Angela
A
Lopes
Janaína Jardim
JJ
Pereira
Patrícia
P
Brum
Clarice
C
Khazzaka
Márcia
M
Vinagre
Anapaula Sommer
AS
D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D003503:Cyclobutanes / Q000494:pharmacology*; D003533:Cyproheptadine / Q000494:pharmacology; D003964:Diaphragm / Q000187:drug effects / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D006003:Glycogen / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D044348:Receptors, Serotonin, 5-HT2 / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013997:Time Factors
D001067:Appetite Depressants; D003503:Cyclobutanes; D003533:Cyproheptadine; D006003:Glycogen; D044348:Receptors, Serotonin, 5-HT2; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C058254:sibutramine