S-14671 Explained

S-14671 is a naphthylpiperazine derivative which acts as a 5-HT_1A receptor agonist (pK_i = 9.3) with high efficacy and exceptional in vivo potency, and also as a 5-HT_2A and 5-HT_2C receptor antagonist (both are pK_i = 7.8).^{[1] [2]} It displays only low and non-significant affinity for 5-HT_1B and 5-HT₃ sites.^[2]

In producing 5-HT_1A-mediated effects such as hypothermia and spontaneous tail flicks in rodents, S-14671 is active at doses as low as 5 μg subcutaneously, and is about 10-fold more potent than 8-OH-DPAT and 100-fold more potent than flesinoxan and buspirone.^{[1] [2]} Other 5-HT_1A-mediated effects of S-14671 include induction of flat-body posture, corticosterone secretion, inhibition of morphine-induced antinociception, and attenuation of the electrical activity of the dorsal raphe nucleus.^[2]

S-14671 has been found to possess powerful efficacy in the rodent forced swim test and in the pigeon conflict test, indicating marked antidepressant and anxiolytic effects, respectively, of which are also 5-HT_1A-mediated.^{[3] [4]} It has never been trialed in humans, perhaps due to its potency being too great.

See also

• CSP-2503
• Naphthylpiperazine

Notes and References

1. Millan MJ, Canton H, Rivet JM, Lejeune F, Laubie M, Lavielle G . S 14671: a novel naphthylpiperazine 5-HT1A agonist of high efficacy and exceptional in vivo potency . European Journal of Pharmacology . 203 . 2 . 319–22 . October 1991 . 1839284 . 10.1016/0014-2999(91)90734-8.
2. Millan MJ, Rivet JM, Canton H, etal . S 14671: a naphtylpiperazine 5-hydroxytryptamine1A agonist of exceptional potency and high efficacy possessing antagonist activity at 5-hydroxytryptamine1C/2 receptors . The Journal of Pharmacology and Experimental Therapeutics . 262 . 2 . 451–63 . August 1992 . 1323650 .
3. Schreiber R, Brocco M, Gobert A, Veiga S, Millan MJ . The potent activity of the 5-HT1A receptor agonists, S 14506 and S 14671, in the rat forced swim test is blocked by novel 5-HT1A receptor antagonists . European Journal of Pharmacology . 271 . 2–3 . 537–41 . December 1994 . 7705455 . 10.1016/0014-2999(94)90816-8.
4. Schreiber R, Brocco M, de Ladonchamps BL, Millan MJ . Involvement of 5-HT1A receptors in the anxiolytic action of S 14671 in the pigeon conflict test . Pharmacology Biochemistry and Behavior . 51 . 2–3 . 211–5 . 1995 . 7667330 . 10.1016/0091-3057(94)00421-E. 32099533 .