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PRX-00023 is a drug of the phenylpiperazine class that was being developed by EPIX Pharmaceuticals Inc for the treatment of generalized anxiety disorder and major depressive disorder. It was well tolerated in clinical trials but failed to reach significant remission on the Hammilton Rating Scales and development was subsequently discontinued.
PRX-00023 acts as a selective 5-HT1A receptor ligand and sigma receptor agonist. Originally believed to have appreciable intrinsic activity as an agonist of the 5-HT1A receptor, later studies found it to possess very low efficacy (6-7% relative to 5-HT) and to behave more like an antagonist, likely underlying its failure as an antidepressant/anxiolytic in clinical trials.
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- 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.
- Rickels K, Mathew S, Banov MD, Zimbroff DL, Oshana S, Parsons EC Jr, Donahue SR, Kauffman M, Iyer GR, Reinhard JF Jr. (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.
- de Paulis T.; Reinhard Jr, 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.
- Mathew SJ, Garakani A, Reinhard JF Jr, 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.
- 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.
- Prof John Kelly (2010). Principles of CNS Drug Development: From Test Tube to Patient. New York: Wiley. ISBN 0-470-51979-7.
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