5-HT2C receptors mediate penile erections in rats: actions of novel and selective agonists and antagonists

Eur J Pharmacol. 1997 Apr 23;325(1):9-12. doi: 10.1016/s0014-2999(97)89962-1.

Abstract

The mixed 5-HT2A/5-HT2B/5-HT2C receptor agonist, m-(chlorophenyl)piperazine (mCPP), elicited penile erections in rats, an action mimicked by the selective 5-HT2C receptor agonist, RO 60-0175 (S)-2-(6-chloro-5-fluoroindol-1-yl)-1-methylethylamine), whereas the preferential 5-HT2B receptor agonist, BW 723C86 (1-[5-(thienylmethoxy)-1H-3-indoyl] propan-2-amine) was ineffective. The actions of mCPP and RO 60-0175 were dose-dependently abolished by the novel 5-HT2B/5-HT2C receptor antagonists, SB 200,646 (1-(1-methylindol-5-yl)-3-(3-pyridyl) urea) and SB 206,553 (5 methyl-1-(3-pyridil-carbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3 -f]indole). In contrast, penile erections were not significantly affected by the selective 5-HT2B receptor antagonist, SB 204,741 (1-(1-methylindol-5-yl)-3-(3-methylisothiazol-5-yl)-urea) nor by the selective 5-HT2A receptor antagonist, MDL 100,907 ([R(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-p iperidine-methanol]). These data provide rigorous pharmacological evidence that activation of 5-HT2C receptor elicits penile erections in the rat. This model should, thus, be of use for characterising novel ligands at this site.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Ethylamines / pharmacology
  • Indoles / pharmacology
  • Male
  • Penile Erection / drug effects*
  • Penile Erection / physiology*
  • Piperazines / pharmacology
  • Pyridines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin / physiology*
  • Serotonin Antagonists / pharmacology*
  • Serotonin Receptor Agonists / pharmacology*
  • Thiophenes / pharmacology
  • Urea / analogs & derivatives
  • Urea / pharmacology

Substances

  • 1-(5-(2-thenyloxy)-1H-indol-3-yl)propan-2-amine
  • Ethylamines
  • Indoles
  • Piperazines
  • Pyridines
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin
  • Ro 60-0175
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Thiophenes
  • N-(1-methyl-5-indolyl)-N'-(3-pyridyl)urea
  • Urea
  • SB 206553
  • 1-(3-chlorophenyl)piperazine