Effect of SB-243213, a selective 5-HT2C receptor antagonist, on the rat sleep profile:: A comparison to paroxetine

5-HT2 receptor antagonists promote slow wave sleep (SWS) in humans and rats, conversely 5-HT2 agonists inhibit SWS in rats. These alterations are thought to be predominantly mediated via the 5-HT2c receptor subtype. It is evident that 5-HT2 receptor function also plays an important role in depression. Here., we examine the acute effect of the selective 5-HT2c receptor antagonist 5-methyl-1-[[-2[(2-methyl-3pyridyl)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-HT2c 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-HT2c receptor antagonists maybe beneficial in the treatment of depress ion/anxiety. (C) 2002 Elsevier Science Inc. All rights reserved.