S 14671 - A NOVEL NAPHTHYLPIPERAZINE 5-HT1A AGONIST OF HIGH EFFICACY AND EXCEPTIONAL INVIVO POTENCY

The novel, naphtylpiperazine 5-HT1A agonist, S 14671 (4-[(thenoyl-2)aminoethyl]-1-(7-methoxynaphtylpiperazine)), displayed very high affinity for 5-HT1A binding sites (pK(i) = 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 hvpothermia and spontaneous tail-flicks at doses as low as greater-than-or-equal-to 5-mu-g/kg s.c. and greater-than-or-equal-to 40-mu-g/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 efficacv and exceptional in vivo potency.