title: Effect of SB-243213, a selective 5-HT(2C) receptor antagonist, on the rat sleep profile: a comparison to paroxetine.
abstract: 5-HT(2) receptor antagonists promote slow wave sleep (SWS) in humans and rats, conversely 5-HT(2) agonists inhibit SWS in rats. These alterations are thought to be predominantly mediated via the 5-HT(2C) receptor subtype. It is evident that 5-HT(2) receptor function also plays an important role in depression. Here, we examine the acute effect of the selective 5-HT(2C) receptor antagonist 5-methyl-1-[[-2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-6-triflouromethylindoline hydrochloride (SB-243213-A) on rat sleep in comparison to the selective serotonin reuptake inhibitor (SSRI) paroxetine. Both SB-243213-A (10 mg/kg po) and paroxetine (3 mg/kg po) significantly increased deep SWS (SWS2) quantity (27% and 24%, respectively) and reduced paradoxical sleep (PS) quantity (35%) during the sleep period. Following SB-243213-A, SWS2 occurrence frequency was reduced (24.1%); however, elevated quantity of SWS2 can be attributed to an increase in occurrence duration (81%). Reduced PS quantity results from a decrease in occurrence frequency (46%). In comparison, paroxetine increased SWS2 occurrence frequency (50%), with decreased frequency (27%) and duration (21%) of PS. The data for SB-243213-A in the present study is consistent with that following ritanserin supporting 5-HT(2C) receptor subtype mediation of this response. The similar effect of SB-243213-A to paroxetine with regard to PS quantity provides further evidence that 5-HT(2C) receptor antagonists maybe beneficial in the treatment of depression/anxiety.
authors.affiliation: Neurology-CEDD, GlaxoSmithKline, New Frontiers Science Park North, Third Avenue, Essex CM19 5AW, Harlow, UK. martin_i_smith@gsk.com
authors.forename: M I
authors.initials: MI
authors.lastname: Smith
authors.forename: D C
authors.initials: DC
authors.lastname: Piper
authors.forename: M S
authors.initials: MS
authors.lastname: Duxon
authors.forename: N
authors.initials: N
authors.lastname: Upton
mesh_terms: D000818:Animals; D001143:Arousal / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D017374:Paroxetine / Q000494:pharmacology*; D017286:Polysomnography / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects*; D012894:Sleep Stages / Q000187:drug effects
chemical_list: D007211:Indoles; D017374:Paroxetine; D011725:Pyridines; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C406343:SB 243213