Naluzotan

Naluzotan (INN, USAN; PRX-00023) is a serotonergic drug of the phenylpiperazine class that was under investigation by EPIX Pharmaceuticals Inc for the treatment of generalized anxiety disorder and major depressive disorder.[1][2] It acts as a selective and potent 5-HT1A receptor partial agonist,[2][3] readily stimulating prolactin responses,[4] though it has also been found to bind to and activate the σ receptor.[5] Naluzotan was well tolerated in clinical trials,[4] with more patients in the control group dropping out due to adverse effects than in the active group in one study.[2] The most frequently reported side effect was headache in 15% of patients (compared to 10% for placebo).[2] In addition, naluzotan demonstrated significant antidepressant and anxiolytic effects as per the HAM-D and MADRS and the HAM-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 to placebo and development was stopped.[7]

Naluzotan
Clinical data
Routes of
administration		Oral[1]
ATC code
  • None
Identifiers
IUPAC name
  • N-(3-{4-[4-(1-cyclohexylmethanesulfonamido)butyl]piperazin-1-yl}phenyl)acetamide
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC23H38N4O3S
Molar mass450.64 g·mol−1
3D model (JSmol)
SMILES
  • O=C(Nc3cccc(N2CCN(CCCCNS(=O)(=O)CC1CCCCC1)CC2)c3)C
InChI
  • 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)

See also
  • Phenylpiperazine

References
  1. de 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. Rickels 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. Iyer 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. Kirchhoff 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.


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