S 14671: a novel naphthylpiperazine 5-HT1A agonist of high efficacy and exceptional in vivo potency.
The novel, naphthylpiperazine 5-HT1A agonist, S 14671 (4-[(thenoyl-2)aminoethyl]-1-(7-methoxynaphtylpiperazine], displayed very high affinity for 5-HT1A binding sites (pKi = 9.3) as compared to the serotonin (5-HT)1A agonists, 8-OH-DPAT (9.2) and (+)-flesinoxan (8.7) and the 5-HT1A partial agonists, buspirone (7.9) and BMY 7378 (8.8). In vivo, S 14671 induced the typical 5-HT1A agonist-induced responses of hypothermia and spontaneous tail-flicks at doses as low as greater than or equal to 5 micrograms/kg s.c. and greater than or equal to 40 micrograms/kg s.c., respectively. In each test, it was about 10-fold more potent than 8-OH-DPAT and 100-fold more potent than (+)-flesinoxan and buspirone. The actions of S 14671 could be blocked by BMY 7378 and the 5-HT1A receptor antagonist, (-)-alprenolol, but not by the 5-HT1C/2 receptor antagonist, ritanserin, nor the 5-HT3 receptor antagonist, ICS 205930. Thus, S 14671 is a novel 5-HT1A ligand of high efficacy and exceptional in vivo potency.
Millan
M J
MJ
FONDAX, Groupe de Recherche Servier, Paris, France.
Canton
H
H
Rivet
J M
JM
Lejeune
F
F
Laubie
M
M
Lavielle
G
G
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000526:Alprenolol / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D008297:Male; D010879:Piperazines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism / Q000502:physiology*; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013876:Thiophenes / Q000378:metabolism / Q000494:pharmacology*
D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C073650:S 14671; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000526:Alprenolol; C053428:BMY 7378