BW-723C86 explained

BW-723C86 is a tryptamine derivative drug which acts as a 5-HT_2B receptor agonist. It has anxiolytic effects in animal studies,^{[1] [2]} and is also used for investigating the function of the 5-HT_2B receptor in a range of other tissues.^{[3] [4] [5]}

BW-723C86 is actually a mixed 5-HT_2B/5-HT_2C agonist, and while it has good selectivity over 5-HT_2A and other serotonin receptor subtypes, it is around only 3 times as selective for 2B compared to 2C and so is much less selective than most research ligands, but no superior 5-HT_2B agonist was available until the potent and selective 5-HT_2B activity of 6-APB was discovered in 2012.^[6] Highly selective 5-HT_2C antagonists are available however, and so a combination of BW-723C86 with a selective 5-HT_2C antagonist allows 5-HT_2B mediated responses to be studied in isolation.

An in vitro study including assay on normal (healthy) human melanocytes found that BW-723C86 causes skin whitening.^[7] The mechanism of action of BW-723C86 is decreasing the expression of MITF which in turn, decreases the expression of the melanin main synthesizing enzymes: tyrosinase, TRP-1 and TRP-2. BW-723C86 is not cytotoxic to melanocytes and, unlike many skin whitening agents, does not directly inhibit the activity of tyrosinase.

See also

• 5-Benzyloxytryptamine
• VU6067416

Notes and References

1. Kennett GA, Bright F, Trail B, Baxter GS, Blackburn TP . Effects of the 5-HT2B receptor agonist, BW 723C86, on three rat models of anxiety . British Journal of Pharmacology . 117 . 7 . 1443–8 . April 1996 . 8730737 . 1909458 . 10.1111/j.1476-5381.1996.tb15304.x .
2. Kennett GA, Trail B, Bright F . Anxiolytic-like actions of BW 723C86 in the rat Vogel conflict test are 5-HT2B receptor mediated . Neuropharmacology . 37 . 12 . 1603–10 . December 1998 . 9886683 . 10.1016/S0028-3908(98)00115-4 . 7310462 .
3. Knowles ID, Ramage AG . Evidence that activation of central 5-HT(2B) receptors causes renal sympathoexcitation in anaesthetized rats . British Journal of Pharmacology . 129 . 1 . 177–83 . January 2000 . 10694218 . 1621132 . 10.1038/sj.bjp.0703011 .
4. Günther S, Maroteaux L, Schwarzacher SW . Endogenous 5-HT2B receptor activation regulates neonatal respiratory activity in vitro . Journal of Neurobiology . 66 . 9 . 949–61 . August 2006 . 16758492 . 10.1002/neu.20253 . 26716284 .
5. Ryan BK, Anwyl R, Rowan MJ . 5-HT2 receptor-mediated reversal of the inhibition of hippocampal long-term potentiation by acute inescapable stress . Neuropharmacology . 55 . 2 . 175–82 . August 2008 . 18538800 . 10.1016/j.neuropharm.2008.05.006 . 17626074 .
6. Iversen L, Gibbons S, Treble R, Setola V, Huang XP, Roth BL. Bryan Roth . Neurochemical profiles of some novel psychoactive substances . European Journal of Pharmacology . 700 . 1–3 . 147–51 . January 2013 . 23261499 . 3582025 . 10.1016/j.ejphar.2012.12.006 .
7. Oh EJ, Park JI, Lee JE, Myung CH, Kim SY, Chang SE, Hwang JS . A Novel Role of Serotonin Receptor 2B Agonist as an Anti-Melanogenesis Agent . International Journal of Molecular Sciences . 17 . 4 . 546 . April 2016 . 27077852 . 4849002 . 10.3390/ijms17040546 . free .