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

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, SE 200,646 (1(1-methylin-dol-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-piperidine-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.