Thermogenic effect of YM348, a novel 5-HT2C-receptor agonist, in rats.
We have investigated the effect of S-2-(7-ethyl-1H-furo[2,3-g]indazol-1-yl)-1-methylethylamine (YM348), a novel 5-HT(2C)-receptor agonist, on body temperature and energy expenditure in Wistar rats. m-Chlorophenylpiperazine (mCPP) and S-2-(6-chloro-5-fluoroindol-1-yl)-1-methylethylamine (RO 60-0175) were used as reference 5-HT(2C)-receptor agonists. Administration of YM348, mCPP and RO 60-0175 dose-dependently and significantly increased body temperature in rats. YM348- or RO 60-0175-induced hyperthermia was significantly attenuated by the non-selective 5-HT(2)-receptor antagonist methysergide and the selective 5-HT(2C)-receptor antagonist SB242084, but not by the selective 5-HT(2A)-receptor antagonist MDL100907. mCPP-induced hyperthermia was significantly attenuated by methysergide, SB242084 and MDL100907. In addition to the increase in body temperature, YM348, mCPP and RO 60-0175 produced dose-related and significant increases in energy expenditure. YM348-, mCPP- and RO 60-0175-induced increases in energy expenditure were significantly attenuated by methysergide and SB242084 but not by MDL100907. These results suggested that 5-HT(2C)-receptor stimulation increased body temperature and energy expenditure and that the 5-HT(2C)-receptor was the target receptor in the thermogenic effect of YM348 in Wistar rats.
Hayashi
Aska
A
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd, 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. hayashi.asuka@yamanouchi.co.jp
Suzuki
Masanori
M
Sasamata
Masao
M
Miyata
Keiji
K
D000818:Animals; D001831:Body Temperature / Q000187:drug effects* / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D007191:Indazoles; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists; C488691:YM348