Effect of SB-243213, a selective 5-HT(2C) receptor antagonist, on the rat sleep profile: a comparison to paroxetine

Pharmacol Biochem Behav. 2002 Apr;71(4):599-605. doi: 10.1016/s0091-3057(01)00702-x.

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Arousal / drug effects
  • Electroencephalography / drug effects
  • Indoles / pharmacology*
  • Male
  • Paroxetine / pharmacology*
  • Polysomnography / drug effects
  • Pyridines / pharmacology*
  • Rats
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin / drug effects*
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Serotonin Antagonists / pharmacology*
  • Sleep / drug effects*
  • Sleep Stages / drug effects

Substances

  • Indoles
  • Pyridines
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Uptake Inhibitors
  • Paroxetine
  • SB 243213