Effects of novel 5-HT1A receptor antagonists on measures of post-synaptic 5-HT1A receptor activation in vivo.
The effects of two putative 5-HT1A antagonists, 4-(2'-methoxyphenyl)-1- [2'-[N-(2"-pyridinyl)-p-iodobenzamido]ethyl]piperazine (p-MPPI) and 4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p- fluorobenzamido]ethyl]piperazine (p-MPPF), were examined in vivo in two tests of postsynaptic 5-HT1A receptor activation, hypothermia and reciprocal forepaw treading, in the rat. Both p-MPPI (10 mg/kg, i.p.) and p-MPPF (10 mg/kg, i.p.) antagonized the hypothermia induced by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.5 mg/kg, s.c.). Neither p-MPPI nor p-MPPF administered alone at a dose of 10 mg/kg (i.p.) induced hypothermia. Similarly, both p-MPPI (10 mg/kg, i.p.) and p-MPPF (2.5 mg/kg, i.p.) completely antagonized 8-OH-DPAT (2 mg/kg, s.c.)-induced forepaw treading in rats pretreated with reserpine (1 mg/kg, s.c., 18-24 hours prior to the experiment). p-MPPI and p-MPPF, at doses of 10 mg/kg (i.p.) did not induce forepaw treading in reserpine pretreated animals. The results of the present study demonstrate that p-MPPI and p-MPPF act as 5-HT1A receptor antagonists in these measures of postsynaptic 5-HT1A receptor activation.
Thielen
R J
RJ
Department of Pharmacology, University of Texas Health Science Center, San Antonio 78284-7764.
Frazer
A
A
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D000631:Aminopyridines; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C087205:4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin