BW-723C86 is atryptamine derivative drug which acts as a5-HT2Breceptoragonist. It hasanxiolytic effects in animal studies,[1][2] and is also used for investigating the function of the 5-HT2B receptor in a range of other tissues.[3][4][5]
BW-723C86 is actually a mixed 5-HT2B/5-HT2C agonist, and while it has good selectivity over 5-HT2A 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-HT2B agonist was available until the potent and selective 5-HT2B activity of6-APB was discovered in 2012.[6] Highly selective 5-HT2C antagonists are available however, and so a combination of BW-723C86 with a selective 5-HT2C antagonist allows 5-HT2B mediated responses to be studied in isolation.
The drug does not induce thehead-twitch response, a behavioral proxy ofpsychedelic effects associated with serotonin5-HT2A receptor agonism, across a wide range of doses.[7] This may be related to the fact that it showed more than 200-fold selectivity for activation of the serotonin 5-HT2B receptor over the serotonin 5-HT2A receptor.[7]
Anin vitro study including assay on normal (healthy) human melanocytes found that BW-723C86 causesskin whitening.[8] The mechanism of action of BW-723C86 is decreasing theexpression ofMITF which in turn, decreases the expression of the melanin main synthesizing enzymes:tyrosinase,TRP-1 andTRP-2.[notes 1] BW-723C86 is not cytotoxic to melanocytes and, unlike many skin whitening agents, does not directlyinhibit the activity of tyrosinase.[notes 2]
^"In summary, results of our study indicated that BW723C86 inhibits melanin synthesis by suppressing the expression of melanogenesis-related proteins (tyrosinase, TRP-1, and TRP-2) at the transcriptional level. The decreased expression of these proteins is a result of reduced MITF expression. Furthermore, the reduced level of MITF was associated with inhibition of the PKA/CREB/MITF pathway and direct inhibition of MITF transcription."[8]: 9
^"BW723C86 treatment reduced melanin content in melan-A cells and in normal human melanocytes (NHM) without affecting cellular viability. BW723C86 reduced intracellular tyrosinase activity but did not affect tyrosinase activity in cell extracts, indicating that BW723C86 does not have a direct effect on tyrosinase activity."[8]: 8
^Kennett GA, Trail B, Bright F (December 1998). "Anxiolytic-like actions of BW 723C86 in the rat Vogel conflict test are 5-HT2B receptor mediated".Neuropharmacology.37 (12):1603–10.doi:10.1016/S0028-3908(98)00115-4.PMID9886683.S2CID7310462.
^abVickers SP, Easton N, Malcolm CS, Allen NH, Porter RH, Bickerdike MJ, Kennett GA (2001). "Modulation of 5-HT(2A) receptor-mediated head-twitch behaviour in the rat by 5-HT(2C) receptor agonists".Pharmacol Biochem Behav.69 (3–4):643–652.doi:10.1016/s0091-3057(01)00552-4.PMID11509227.
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