Roxindole

Roxindole
Systematic (IUPAC) name
3-[4-(4-phenyl-3,6-dihydro-2H-pyridin-1-yl)butyl]-1H-indol-5-ol
Clinical data
Pregnancy cat.  ?
Legal status  ?
Identifiers
CAS number 112192-04-8
ATC code None
PubChem CID 219050
IUPHAR ligand 52
ChemSpider 189880
UNII 43227SMS0O Y
Chemical data
Formula C23H26N2O 
Mol. mass 346.47 g/mol
SMILES eMolecules & PubChem

Roxindole (EMD-49,980) is a dopaminergic and serotonergic drug which was originally developed 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][4] It has also been investigated as a therapy for Parkinson's disease and prolactinoma.[5][6]

Roxindole acts as an agonist at the following receptors:[7][8]

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] 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][11]

References

  1. ^ a b 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. 
  2. ^ a b 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. ^ a b 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 : the Journal of the European College of Neuropsychopharmacology 2 (1): 91–5. doi:10.1016/0924-977X(92)90041-6. PMID 1353388. http://linkinghub.elsevier.com/retrieve/pii/0924-977X(92)90041-6. 
  4. ^ a b Maj J, Kolodziejczyk K, Rogóz Z, Skuza G (1996). "Roxindole, a potential antidepressant. I. Effect on the dopamine system". Journal of Neural Transmission (Vienna, Austria : 1996) 103 (5): 627–41. PMID 8811507. 
  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 : Official Journal of the Movement Disorder Society 8 (2): 195–7. doi:10.1002/mds.870080214. PMID 8097280. 
  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. PMID 7950157. 
  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. PMID 10431754. http://link.springer.de/link/service/journals/00210/bibs/9359006/93590447.htm. 
  8. ^ a b 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. ^ a b 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. http://linkinghub.elsevier.com/retrieve/pii/0014-2999(89)90651-1. 
  10. ^ a b 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): 41–8. PMID 8558454. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8558454. 
  11. ^ 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. 
GABAA PAMs
Abecarnil • Adipiplon • Alpidem • CGS-8216 • CGS-9896 • CGS-13767 • CGS-20625 • Divaplon • ELB-139 • Fasiplon • GBLD-345 • Gedocarnil • L-838,417 • NS-2664 • NS-2710 • Ocinaplon • Pagoclone • Panadiplon • Pipequaline • RWJ-51204 • SB-205,384 • SL-651,498 • Taniplon • TP-003 • TP-13 • TPA-023 • Y-23684 • ZK-93423
Others
α2δ VDCC Blockers
5-HT1A Agonists
Azapirones: Buspirone • Gepirone • Tandospirone; Others: Flesinoxan • Oxaflozane
H1 Antagonists
Diphenylmethanes: Captodiame • Hydroxyzine; Others: Brompheniramine • Chlorpheniramine • Pheniramine
CRH1 Antagonists
NK2 Antagonists
MCH1 antagonists
mGluR2/3 Agonists
mGluR5 NAMs
TSPO agonists
σ1 agonists
Others

M: PSO/PSI

mepr

dsrd (o, p, m, p, a, d, s), sysi/epon, spvo

proc(eval/thrp), drug(N5A/5B/5C/6A/6B/6D)
Antipsychotics (neuroleptics) (N05A)
Typical
Benzamides: Levosulpiride • Nemonapride • Sulpiride • Sultopride • Tiapride • Veralipride; Butyrophenones: Azaperone • Benperidol • Bromperidol • Droperidol • Fluanisone • Haloperidol • Lenperone • Moperone • Pipamperone • Spiperone • Timiperone • Trifluperidol; Diphenylbutylpiperidines: Clopimozide • Fluspirilene • Penfluridol • Pimozide; Phenothiazines: Acepromazine • Acetophenazine • Butaperazine • Carphenazine • Chloracizine • Chlorproethazine • Chlorpromazine • Cyamemazine • Dixyrazine • Fluacizine • Fluphenazine • Levomepromazine/Methotrimeprazine • Mesoridazine • Perazine • Pericyazine • Perphenazine • Piperacetazine • Pipotiazine • Prochlorperazine • Promazine • Promethazine • Propiomazine • Sulforidazine • Thiethylperazine • Thiopropazate • Thioproperazine • Thioridazine • Trifluoperazine • Triflupromazine; Thioxanthenes: Chlorprothixene • Clopenthixol • Flupentixol • Thiothixene • Zuclopenthixol; Tricyclics: Amoxapine • Butaclamol • Fluotracen • Loxapine • Trimipramine; Others: Prothipendyl
Atypical
Others

M: PSO/PSI

mepr

dsrd (o, p, m, p, a, d, s), sysi/epon, spvo

proc(eval/thrp), drug(N5A/5B/5C/6A/6B/6D)
Dopaminergics
Anticholinergics
Others

M: CNS

anat(n/s/m/p/4/e/b/d/c/a/f/l/g)/phys/devp

noco(m/d/e/h/v/s)/cong/tumr, sysi/epon, injr

proc, drug(N1A/2AB/C/3/4/7A/B/C/D)