生物活性

• 描述Paliperidone is a second-generation antipsychotic drug belonging to the class of benzisoxasole derivatives. Paliperidone is the major active metabolite of risperidone (9-OH-risperidone) and, as such, is comparable to the latter in terms of pharmacodynamic properties^[3]. Paliperidone has demonstrated efficacy in the reduction of acute schizophrenia symptoms and clinical benefits were maintained also in the long-term treatments. Paliperidone ER (extended-release) and PP (paliperidone palmitate) are generally well tolerated with a predictable adverse event profile^[4]. Paliperidone inhibited MK-801 induced neurotoxicity both in MTT metabolism assay and in lactate dehydrogenase (LDH) activity assay. Time course studies revealed that paliperidone effectively attenuated the elevation of intracellular free calcium concentration ([Ca(2+)]i) induced by exposure to MK-801. Moreover, paliperidone could significantly retard MK-801-mediated inhibition of neurite outgrowth and reverse MK-801-induced decreases of gene expression and phosphorylation of Akt1 and GSK3β^[5]. Moreover, paliperidone works finely at low concentrations (10 and 50 μM) against Aβ(25-35) and MPP(+) and solely protected SH-SY5Y from hydrogen peroxide. At 100 μM, paliperidone completely diminished cell reduction induced by different stressors, regardless of their dosages. Paliperidone was demonstrated with a higher oxidative stress-scavenging properties than other APDs (Antipsychotic drugs) in several aspects, such as generated bulk glutathione, low HNE, and protein carbonyl productions^[6].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT01742390	Sexual Dysfunction ... more >> Hyperprolactinemia Collapse <<	Phase 4	Unknown	June 2014	China, Beijing ... more >> Institute of mental health, Peking University Not yet recruiting Beijing, Beijing, China, 100191 Contact: Tianmei Si, MD.    8610-82801948    si.tian-mei@163.cm    Principal Investigator: Tianmei Si, MD.          China, Hebei The first hospital of Hebei Province University Recruiting Shijiazhuang, Hebei, China, 050000 Contact: Xueyi Wang, Professor    0311-85917290       Sub-Investigator: Xueyi Wang Collapse <<
  NCT00589914	Schizophrenia	Phase 3	Completed	-	-
  NCT02532842	-	-	Completed	-	Croatia ... more >> Rijeka, Croatia Split, Croatia Zagreb, Croatia Russian Federation Moscow, Russian Federation St Petersburg N/A, Russian Federation St-Petersburg, Russian Federation Turkey Ankara, Turkey Denizli, Turkey Collapse <<

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• 参考文献

• [1] Zhu HJ, Wang JS, et al. Risperidone and paliperidone inhibit p-glycoprotein activity in vitro. Neuropsychopharmacology. 2007 Apr;32(4):757-64.

  [2] Woestenborghs R, Lorreyne W, et al. Determination of risperidone and 9-hydroxyrisperidone in plasma, urine and animal tissues by high-performance liquid chromatography. J Chromatogr. 1992 Dec 2;583(2):223-30.

  [3] Valsecchi P, Garozzo A, Nibbio G, et al. Paliperidone extended-release in the short- and long-term treatment of schizophrenia. Riv Psichiatr. 2019;54(2):43‐58

  [4] Mauri MC, Reggiori A, Paletta S, Di Pace C, Altamura AC. Paliperidone for the treatment of schizophrenia and schizoaffective disorders - a drug safety evaluation. Expert Opin Drug Saf. 2017;16(3):365‐379

  [5] Peng L, Zhu D, Feng X, et al. Paliperidone protects prefrontal cortical neurons from damages caused by MK-801 via Akt1/GSK3β signaling pathway. Schizophr Res. 2013;147(1):14‐23

  [6] Yang MC, Lung FW. Neuroprotection of paliperidone on SH-SY5Y cells against β-amyloid peptide(25-35), N-methyl-4-phenylpyridinium ion, and hydrogen peroxide-induced cell death. Psychopharmacology (Berl). 2011;217(3):397‐410

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