Roxindole

Roxindole (developmental code name EMD-49980) is a dopaminergic and serotonergic drug which was originally developed by Merck KGaA for the treatment of schizophrenia.^[1][2][3] In clinical trials its antipsychotic efficacy was only modest but it was unexpectedly found to produce potent and rapid antidepressant and anxiolytic effects.^[2][3] As a result, roxindole was further researched for the treatment of depression instead.^[1][4] It has also been investigated as a therapy for Parkinson's disease and prolactinoma.^[5][6] However, it has never been marketed.^[7]

Roxindole

Clinical data
Other names	EMD-49980; EMD49980
ATC code	None
Identifiers
IUPAC name 3-[4-(4-phenyl-3,6-dihydro-2H-pyridin-1-yl)butyl]-1H-indol-5-ol
CAS Number	112192-04-8
PubChem CID	219050
IUPHAR/BPS	52
ChemSpider	189880
UNII	43227SMS0O
CompTox Dashboard (EPA)	DTXSID5043895
Chemical and physical data
Formula	C23H26N2O
Molar mass	346.474 g·mol−1
3D model (JSmol)	Interactive image
SMILES Oc1ccc2c(c1)c(c[nH]2)CCCCN4C/C=C(/c3ccccc3)CC4

Roxindole acts as an agonist at the following receptors:^[8][9]

• D₂ receptor (K_i = 2.82 nM)
• D₃ receptor (K_i = 1.17 nM)
• D₄ receptor (K_i = 5.89 nM)
• 5-HT_1A receptor (K_i = 0.380 nM)

At D₂ and possibly D₃ receptors roxindole is a partial agonist with preferential actions at autoreceptors and has been touted as a 'selective' autoreceptor agonist, hence the justification of its application as an antipsychotic.^[10][11] Weaker activity at the serotonin 1_B and 1_D receptors has been seen.^[12] It is also a serotonin reuptake inhibitor (IC₅₀ = 1.4 nM) and has been reported to act as a 5-HT_2A receptor antagonist as well.^{[9][10][11][13]}