S 14671: a novel naphthylpiperazine 5-HT1A agonist of high efficacy and exceptional in vivo potency.

Abstract

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.

• Authors: M J Millan, H Canton, J M Rivet, F Lejeune, M Laubie, G Lavielle
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 203 Issue 2 Pg. 319-22 (Oct 15 1991) ISSN: 0014-2999 [Print] Netherlands
• PMID: 1839284 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Piperazines
• Receptors, Serotonin
• Serotonin Antagonists
• Tetrahydronaphthalenes
• Thiophenes
• S 14671
• 8-Hydroxy-2-(di-n-propylamino)tetralin
• Alprenolol
• BMY 7378

Topics

• 8-Hydroxy-2-(di-n-propylamino)tetralin
• Alprenolol (pharmacology)
• Animals
• Behavior, Animal (drug effects)
• Binding, Competitive
• Dose-Response Relationship, Drug
• Male
• Piperazines (metabolism, pharmacology)
• Rats
• Rats, Inbred Strains
• Receptors, Serotonin (metabolism, physiology)
• Serotonin Antagonists
• Tetrahydronaphthalenes (pharmacology)
• Thiophenes (metabolism, pharmacology)