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Naluzotan

From Wikipedia, the free encyclopedia
Chemical compound
Pharmaceutical compound
Naluzotan
Clinical data
Routes of
administration
Oral[1]
ATC code
  • None
Identifiers
  • N-(3-{4-[4-(1-cyclohexylmethanesulfonamido)butyl]piperazin-1-yl}phenyl)acetamide
CAS Number
PubChemCID
ChemSpider
UNII
CompTox Dashboard(EPA)
Chemical and physical data
FormulaC23H38N4O3S
Molar mass450.64 g·mol−1
3D model (JSmol)
  • O=C(Nc3cccc(N2CCN(CCCCNS(=O)(=O)CC1CCCCC1)CC2)c3)C
  • InChI=1S/C23H38N4O3S/c1-20(28)25-22-10-7-11-23(18-22)27-16-14-26(15-17-27)13-6-5-12-24-31(29,30)19-21-8-3-2-4-9-21/h7,10-11,18,21,24H,2-6,8-9,12-17,19H2,1H3,(H,25,28)
  • Key:SPWZXWDPAWDKQE-UHFFFAOYSA-N
  (verify)

Naluzotan (INN,USAN;PRX-00023) is aserotonergicdrug of thephenylpiperazine class that was under investigation byEPIX Pharmaceuticals Inc for the treatment ofgeneralized anxiety disorder andmajor depressive disorder.[1][2] It acts as aselective andpotent5-HT1Areceptorpartial agonist,[2][3] readily stimulatingprolactin responses,[4] though it has also been found to bind to and activate theσ receptor.[5]

Clinical trials

[edit]

Naluzotan was well tolerated inclinical trials,[4] with more patients in the control group dropping out due toadverse effects than in the active group in one study.[2] The most frequently reported side effect washeadache in 15% of patients (compared to 10% for placebo).[2]

In addition, naluzotan demonstrated significantantidepressant andanxiolytic effects as per theHAM-D andMADRS and theHAM-A, respectively, in some trials,[2] but in others it did not.[6][7] In the end it was not found to be significantly superior enough toplacebo and development was stopped.[7]

See also

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References

[edit]
  1. ^abde Paulis T (2007). "Drug evaluation: PRX-00023, a selective 5-HT1A receptor agonist for depression".Curr Opin Investig Drugs.8 (1):78–86.PMID 17263189.
  2. ^abcdeRickels K, Mathew S, Banov MD, Zimbroff DL, Oshana S, Parsons EC, Donahue SR, Kauffman M, Iyer GR, Reinhard JF (2008). "Effects of PRX-00023, a novel, selective serotonin 1A receptor agonist on measures of anxiety and depression in generalized anxiety disorder: results of a double-blind, placebo-controlled trial".J Clin Psychopharmacol.28 (2):235–239.doi:10.1097/JCP.0b013e31816774de.PMID 18344738.S2CID 40515142.
  3. ^Becker OM, Dhanoa DS, Marantz Y, Chen D, Shacham S, Cheruku S, Heifetz A, Mohanty P, Fichman M, Sharadendu A, Nudelman R, Kauffman M, Noiman S (2006). "An integrated in silico 3D model-driven discovery of a novel, potent, and selective amidosulfonamide 5-HT1A agonist (PRX-00023) for the treatment of anxiety and depression".J Med Chem.49 (11):3116–3135.doi:10.1021/jm0508641.PMID 16722631.
  4. ^abIyer GR, Reinhard JF, Oshana S, Kauffman M, Donahue S (2007). "Tolerability, pharmacokinetics, and neuroendocrine effects of PRX-00023, a novel 5-HT1A agonist, in healthy subjects".J Clin Pharmacol.47 (7):817–824.doi:10.1177/0091270007300953.PMID 17495280.S2CID 30536648.
  5. ^Prof John Kelly (2010).Principles of CNS Drug Development: From Test Tube to Patient. New York: Wiley.ISBN 978-0-470-51979-0.
  6. ^Mathew SJ, Garakani A, Reinhard JF, Oshana S, Donahue S (2008). "Short-term tolerability of a nonazapirone selective serotonin 1A agonist in adults with generalized anxiety disorder: a 28-day, open-label study".Clin. Ther.30 (9):1658–1666.doi:10.1016/j.clinthera.2008.09.006.PMID 18840371.
  7. ^abKirchhoff VD, Nguyen HT, Soczynska JK, Woldeyohannes H, McIntyre RS (October 2009)."Discontinued psychiatric drugs in 2008".Expert Opinion on Investigational Drugs.18 (10):1431–43.doi:10.1517/13543780903184591.PMID 19715445.S2CID 34201544.
5-HT1
5-HT1A
5-HT1B
5-HT1D
5-HT1E
5-HT1F
5-HT2
5-HT2A
5-HT2B
5-HT2C
5-HT37
5-HT3
5-HT4
5-HT5A
5-HT6
5-HT7
σ1
σ2
Unsorted
Phenylpiperazines
Benzylpiperazines
Naphthylpiperazines
Quinolinylpiperazines
Diphenylalkylpiperazines
Pyrimidinylpiperazines
Pyridinylpiperazines
Benzo(iso)thiazolylpiperazines
Tricyclic-linked piperazines
Others/uncategorized
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