WAY-100135 explained

WAY-100135 is a serotonergic drug of the phenylpiperazine family which is used in scientific research.^[1] It acts as potent 5-HT_1A receptor antagonist,^[2] and was originally believed to be highly selective, but further studies have demonstrated that it also acts as a partial agonist of the 5-HT_1D receptor (pK_i = 7.58; virtually the same affinity for 5-HT_1A), and to a much lesser extent, of the 5-HT_1B receptor (pK_i = 5.82).^[3] These findings may have prompted the development of the related compound WAY-100635, another purportedly selective and even more potent 5-HT_1A antagonist, which was synthesized shortly thereafter.^[4] However, WAY-100635 turned out to be non-selective as well, having been shown to act additionally as a potent D₄ receptor agonist later on.^[5]

See also

• WAY-100635

Notes and References

1. Fletcher A, Bill DJ, Bill SJ, etal . WAY100135: a novel, selective antagonist at presynaptic and postsynaptic 5-HT1A receptors . European Journal of Pharmacology . 237 . 2–3 . 283–91 . June 1993 . 8365456 . 10.1016/0014-2999(93)90280-u.
2. Cliffe IA, Brightwell CI, Fletcher A, etal . (S)-N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide [(S)-WAY-100135]: a selective antagonist at presynaptic and postsynaptic 5-HT1A receptors . Journal of Medicinal Chemistry . 36 . 10 . 1509–10 . May 1993 . 8496920 . 10.1021/jm00062a028.
3. Davidson C, Ho M, Price GW, Jones BJ, Stamford JA . (+)-WAY 100135, a partial agonist, at native and recombinant 5-HT1B/1D receptors . . 121 . 4 . 737–42 . June 1997 . 9208142 . 1564750 . 10.1038/sj.bjp.0701197 .
4. Fornal CA, Metzler CW, Gallegos RA, Veasey SC, McCreary AC, Jacobs BL . WAY-100635, a potent and selective 5-hydroxytryptamine1A antagonist, increases serotonergic neuronal activity in behaving cats: comparison with (S)-WAY-100135 . The Journal of Pharmacology and Experimental Therapeutics . 278 . 2 . 752–62 . August 1996 . 8768728 .
5. Bryan Roth . Chemel BR, Roth BL, Armbruster B, Watts VJ, Nichols DE . WAY-100635 is a potent dopamine D4 receptor agonist . Psychopharmacology . 188 . 2 . 244–51 . October 2006 . 16915381 . 10.1007/s00213-006-0490-4 . 24194034 .