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, 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.
Millan
M J
MJ
Institut de Recherches Servier, Centre de Recherches de Croissy, Department of Psychopharmacology, Croissy-sur-Seine (Paris), France.
Peglion
J L
JL
Lavielle
G
G
Perrin-Monneyron
S
S
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005021:Ethylamines / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D010410:Penile Erection / Q000187:drug effects* / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
C092430:1-(5-(2-thenyloxy)-1H-indol-3-yl)propan-2-amine; D005021:Ethylamines; D007211:Indoles; D010879:Piperazines; D011725:Pyridines; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; C103848:Ro 60-0175; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013876:Thiophenes; C080864:N-(1-methyl-5-indolyl)-N'-(3-pyridyl)urea; D014508:Urea; C094868:SB 206553; C015068:1-(3-chlorophenyl)piperazine