Roxindole
Dopaminergic & serotonergic drug developed for schizophrenia treatment / From Wikipedia, the free encyclopedia
Roxindole (EMD-49,980) 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]
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Formula | C23H26N2O |
Molar mass | 346.474 g·mol−1 |
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Roxindole acts as an agonist at the following receptors:[7][8]
- D2 receptor (pKi = 8.55)
- D3 receptor (pKi = 8.93)
- D4 receptor (pKi = 8.23)
- 5-HT1A receptor (pKi = 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.[9][10] Weaker activity at the serotonin 1B and 1D receptors has been seen.[11] It is also a serotonin reuptake inhibitor (IC50 = 1.4 nM) and has been reported to act as a 5-HT2A receptor antagonist as well.[8][9][10][12]
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.