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Roxindole

Clinical data
ATC code	none
Identifiers
IUPAC name 3--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
3D model (JSmol)	Interactive image
SMILES Oc1ccc2c(c1)c(c2)CCCCN4C/C=C(/c3ccccc3)CC4

Roxindole (EMD-49,980) is a dopaminergic and serotonergic drug which was originally developed by Merck KGaA for the treatment of schizophrenia. In clinical trials its antipsychotic efficacy was only modest but it was unexpectedly found to produce potent and rapid antidepressant and anxiolytic effects. As a result, roxindole was further researched for the treatment of depression instead. It has also been investigated as a therapy for Parkinson's disease and prolactinoma.

Roxindole acts as an agonist at the following receptors:

• D₂ receptor (pK_i = 8.55)
• D₃ receptor (pK_i = 8.93)
• D₄ receptor (pK_i = 8.23)
• 5-HT_1A receptor (pK_i = 9.42)

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. Weaker activity at the serotonin 1_B and 1_D receptors has been seen. 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.

References

1. ^ Gründer G, Wetzel H, Hammes E, Benkert O (1993). "Roxindole, a dopamine autoreceptor agonist, in the treatment of major depression". Psychopharmacology. 111 (1): 123–6. doi:10.1007/BF02257418. PMID 7870927. S2CID 8154586.
2. ^ Klimke A, Klieser E (July 1991). "Antipsychotic efficacy of the dopaminergic autoreceptor agonist EMD 49980 (Roxindol). Results of an open clinical study". Pharmacopsychiatry. 24 (4): 107–12. doi:10.1055/s-2007-1014451. PMID 1684439.
3. ^ Kasper S, Fuger J, Zinner HJ, Bäuml J, Möller HJ (March 1992). "Early clinical results with the neuroleptic roxindole (EMD 49,980) in the treatment of schizophrenia--an open study". European Neuropsychopharmacology. 2 (1): 91–5. doi:10.1016/0924-977X(92)90041-6. PMID 1353388. S2CID 21861347.
4. Maj J, Kolodziejczyk K, Rogóz Z, Skuza G (1996). "Roxindole, a potential antidepressant. I. Effect on the dopamine system". Journal of Neural Transmission. 103 (5): 627–41. doi:10.1007/bf01273159. PMID 8811507. S2CID 33701841.
5. Bravi D, Davis TL, Mouradian MM, Chase TN (April 1993). "Treatment of Parkinson's disease with the partial dopamine agonist EMD 49980". Movement Disorders. 8 (2): 195–7. doi:10.1002/mds.870080214. PMID 8097280. S2CID 23676084.
6. Jaspers C, Benker G, Reinwein D (June 1994). "Treatment of prolactinoma patients with the new non-ergot dopamine agonist roxindol: first results". The Clinical Investigator. 72 (6): 451–6. doi:10.1007/bf00180520. PMID 7950157. S2CID 532184.
7. Newman-Tancredi A, Cussac D, Audinot V, Millan MJ (June 1999). "Actions of roxindole at recombinant human dopamine D2, D3 and D4 and serotonin 5-HT1A, 5-HT1B and 5-HT1D receptors". Naunyn-Schmiedeberg's Archives of Pharmacology. 359 (6): 447–53. doi:10.1007/pl00005374. PMID 10431754. S2CID 19721911. Archived from the original on 2013-02-11.
8. ^ Heinrich T, Böttcher H, Bartoszyk GD, Greiner HE, Seyfried CA, Van Amsterdam C (September 2004). "Indolebutylamines as selective 5-HT(1A) agonists". Journal of Medicinal Chemistry. 47 (19): 4677–83. doi:10.1021/jm040792y. PMID 15341483.
9. ^ Seyfried CA, Greiner HE, Haase AF (January 1989). "Biochemical and functional studies on EMD 49,980: a potent, selectively presynaptic D-2 dopamine agonist with actions on serotonin systems". European Journal of Pharmacology. 160 (1): 31–41. doi:10.1016/0014-2999(89)90651-1. PMID 2565817.
10. ^ Bartoszyk GD, Harting J, Minck KO (January 1996). "Roxindole: psychopharmacological profile of a dopamine D2 autoreceptor agonist". The Journal of Pharmacology and Experimental Therapeutics. 276 (1): 41–48. PMID 8558454.
11. Newman-Tancredi A, Cussac D, Audinot V, Millan MJ (June 1999). "Actions of roxindole at recombinant human dopamine D2, D3 and D4 and serotonin 5-HT1A, 5-HT1B and 5-HT1D receptors". Naunyn-Schmiedeberg's Archives of Pharmacology. 359 (6): 447–453. doi:10.1007/pl00005374. PMID 10431754. S2CID 19721911.
12. Maj J, Kołodziejczyk K, Rogóz Z, Skuza G (March 1997). "Roxindole, a dopamine autoreceptor agonist with a potential antidepressant activity. II. Effects on the 5-hydroxytryptamine system". Pharmacopsychiatry. 30 (2): 55–61. doi:10.1055/s-2007-979483. PMID 9131725.

• Drugs not assigned an ATC code
• Indoles
• Tetrahydropyridines
• Hydroxyarenes
• Drugs developed by Merck