WAY 100,135 and (-)-tertatolol act as antagonists at both 5-HT1A autoreceptors and postsynaptic 5-HT1A receptors in vivo.
In binding studies, WAY 100,135 (N-tertiobutyl-3-[4-(2-methoxyphenyl)-piperazinyl]-2-phenylpropana mide) and (-)-tertatolol showed affinities (Ki) of 29 nM and 10 nM, respectively, at 5-HT1A receptors. In vivo, they both dose dependently blocked the flat-body posture and corticosterone secretion provoked by an action of the 5-HT1A receptor agonist, S 14671 (1-[2-(2-thenoyl-amino)ethyl]-4-[1-(7- methoxynaphtyl)]piperazine), at postsynaptic 5-HT1A receptors. Alone, they exerted little effect. The firing rate of dorsal raphe neurones, which bear inhibitory 5-HT1A autoreceptors, was reduced by S 14671 whereas it was not affected by WAY 100,135 and was increased by (-)-tertatolol. Both WAY 100,135 and (-)-tertatolol blocked the ability of S 14671 to inhibit raphe firing. In conclusion, these data demonstrate that WAY 100,135 and (-)-tertatolol behave as antagonists at both 5-HT1A autoreceptors and postsynaptic 5-HT1A receptors in vivo.
Lejeune
F
F
Department of Psychopharmacology, Institut de Recherches Servier (I.D.R.S.), Puteaux, France.
Rivet
J M
JM
Gobert
A
A
Canton
H
H
Millan
M J
MJ
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D003345:Corticosterone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D010879:Piperazines / Q000378:metabolism / Q000494:pharmacology*; D011412:Propanolamines / Q000378:metabolism / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013237:Stereoisomerism; D013876:Thiophenes / Q000494:pharmacology
D010879:Piperazines; D011412:Propanolamines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013876:Thiophenes; C081293:WAY 100135; C073650:S 14671; C005632:tertatolol; D003345:Corticosterone