Iloperidone: A new benzisoxazole atypical antipsychotic drug. Is it novel enough to impact the crowded atypical antipsychotic market?

Expert Opinion on Investigational Drugs

Volumn 17, Issue 1, 2008, Pages 61-75

  Albers, Lawrence James ^a   Musenga, Alessandro ^b   Raggi, Maria Augusta ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

Atypical antipsychotic; Iloperidone; Pharmacodynamics; Pharmacokinetics; Schizophrenia treatment; Therapeutic drug monitoring

Indexed keywords

ARIPIPRAZOLE; ASENAPINE; ATYPICAL ANTIPSYCHOTIC AGENT; BENZAMIDE DERIVATIVE; BIFEPRUNOX; BLONANSERIN; BUTYROPHENONE DERIVATIVE; CHLORPROMAZINE; CLOZAPINE; FLUOXETINE; HALOPERIDOL; ILOPERIDONE; NEUROLEPTIC AGENT; OLANZAPINE; PALIPERIDONE; PHENOTHIAZINE DERIVATIVE; PLACEBO; QUETIAPINE; RISPERIDONE; SERTINDOLE; THIOXANTHENE DERIVATIVE; ZIPRASIDONE; ADRENERGIC RECEPTOR; DOPAMINE RECEPTOR; ISOXAZOLE DERIVATIVE; PIPERIDINE DERIVATIVE; SEROTONIN RECEPTOR;

AGITATION; AGRANULOCYTOSIS; AKATHISIA; ANXIETY; BALANCE DISORDER; BINDING AFFINITY; BIPOLAR DISORDER; BLOOD PRESSURE; CARDIOVASCULAR DISEASE; CATALEPSY; CLINICAL TRIAL; CONSTIPATION; DIABETES MELLITUS; DIZZINESS; DOSE RESPONSE; DROWSINESS; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG DOSE COMPARISON; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG FECES LEVEL; DRUG INDUCED HEADACHE; DRUG INHIBITION; DRUG MEGADOSE; DRUG METABOLISM; DRUG MONITORING; DRUG OVERDOSE; DRUG PROTEIN BINDING; DRUG RECEPTOR BINDING; DRUG SAFETY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TOLERABILITY; DRUG WITHDRAWAL; EVIDENCE BASED MEDICINE; EXTRAPYRAMIDAL SYMPTOM; FATIGUE; FOOD; FOOD DRUG INTERACTION; GASTROINTESTINAL DISEASE; HEART ARRHYTHMIA; HEART DISEASE; HEART RATE; HUMAN; HYPERLIPIDEMIA; HYPERPROLACTINEMIA; INSOMNIA; IRRITABILITY; LETHARGY; MAXIMUM TOLERATED DOSE; METABOLIC SYNDROME X; NAUSEA; NONHUMAN; NOSE CONGESTION; ORTHOSTATIC BLOOD PRESSURE; ORTHOSTATIC HYPOTENSION; PATIENT COMPLIANCE; PHARMACODYNAMICS; PHARMACOGENETICS; QT INTERVAL; QT PROLONGATION; QUALITY OF LIFE; REVIEW; RISK BENEFIT ANALYSIS; SCHIZOPHRENIA; SEDATION; SEIZURE; SIDE EFFECT; SINGLE DRUG DOSE; SOMNOLENCE; STRUCTURE ACTIVITY RELATION; SYNCOPE; SYSTOLIC BLOOD PRESSURE; TACHYCARDIA; TARDIVE DYSKINESIA; TREMOR; VOMITING; WEIGHT GAIN; XEROSTOMIA; ANIMAL; CHEMISTRY; DRUG DESIGN; DRUG SCREENING; ECONOMICS; MARKETING; METABOLISM;

ANIMALS; ANTIPSYCHOTIC AGENTS; CLINICAL TRIALS AS TOPIC; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; HUMANS; ISOXAZOLES; MARKETING; PIPERIDINES; RECEPTORS, ADRENERGIC; RECEPTORS, DOPAMINE; RECEPTORS, SEROTONIN; SCHIZOPHRENIA; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 38949090435     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.17.1.61     Document Type: Review

References (88)

1. Akhondzadeh S. Pharmacotherapy of schizophrenia: the past, present and future. Curr Drug Ther 2006;1:1-7
2. McGrath JJ. Variations in the incidence of schizophrenia: data versus dogma. Schizophr Bull 2006;32:195-7
3. Bernardo M, Azanza JR, Rubio-Terres C, Rejas J. Cost-effectiveness analysis of schizophrenia relapse prevention. An economic evaluation of the ZEUS (Ziprasidone-Extended-Use-In-Schizophrenia) study in Spain. Clin Drug Invest 2006;26:447-57
4. Stahl SM. Psychopharmacology of antipsychotics. London: Martin Dunitz; 1999
5. Freedman R. Schizophrenia. N Engl J Med 2003;349:1738-49
6. Rosenheck R, Cramer J, Xu W, et al. A comparison of clozapine and haloperidol in hospitalized patients with refractory schizophrenia. N Engl J Med 1997;337:809-15
7. Di Forti M, Lappin JM, Murray RM. Risk factors for schizophrenia - all roads lead to dopamine. Eur Neuropsychopharm 2007;17:S101-S107
8. Raggi MA. Pharmacological treatment of schizophrenia: recent antipsychotic drugs and new therapeutic strategies. Current Medicinal Chemistry. Raggi MA, editor. Chicago: Bentham Publisher; 2004; p. 1-396
9. Meltzer HY. Role of serotonin in the action of atypical antipsychotic drugs. Clin Neurosci 1995;3:64-75
10. Singh AN. Trend of new antipsychotics in development for schizophrenia. Int Med J 2005;12:175-80
11. Raggi MA, Mandrioli R, Sabbioni C, Pucci V. Atypical antipsychotics: pharmacokinetics, therapeutic drug monitoring and pharmacological interactions. Curr Med Chem 2004;11:279-96
12. Emsley RA. Partial response to antipsychotic treatment: the patient with enduring symptoms. J Clin Psych 1999;60(Suppl 23):10-3
13. Martindale - The Complete Drug Reference. Sweetman SC, editor. London: Pharmaceutical Press; 2004; p. 675-8
14. Meltzer HY, Matsubara S, Lee JC. The ratios of serotonin2 and dopamine2 affinities differentiate atypical and typical antipsychotic drugs. Psychopharmacol Bull 1989;25:390-2
15. Raggi MA. Therapeutic drug monitoring: chemical-clinical correlations of atypical antipsychotic drugs. Curr Med Chem 2002;9:1397-409
16. Conley RR, Kelly DL. A review of current drug targets and pharmacology of antipsychotic treatment. Med Chem Rev 2005;2:177-82
17. Friedman JI, Temporini H, Davis KL. Pharmacologic strategies for augmenting cognitive performance in schizophrenia. Biol Psychiatry 1999;45:1-16
18. Rithelson E, Souder T. Binding of antipsychotic drugs to human brain receptors-focus on newer generation compounds. Life Sci 2000;68:29-39
19. Bymaster FP, Felder CC, Tzavara E, et al. Muscarinic mechanisms of antipsychotic atypicality. Progr Neuro-Psychoph 2003;27:1125-43
20. Ananth J, Parameswaran S, Gunatilake S. Side effects of atypical antipsychotic drugs. Curr Pharm, Design 2004;10:2219-29
21. Dorado P, Berect R, Penas-Lledo EM, Llerena A. Antipsychotic drugs and QTc prolongation: the potential role of CYP2D6 genetic polymorphism. Expert Opin Drug Metab Toxicol 2007;3:9-19
22. Martindale - The Complete Drug Reference. Sweetman SC, editor. London: Pharmaceutical Press; 2004. p. 685-9
23. Yoshimura R, Ueda N, Nakamura J. Possible relationship between combined plasma concentrations of risperidone plus 9-hydroxyrisperidone and extrapyramidal symptoms. Neuropsychobiology 2001;44:129-33
24. Pajonk FG. Risperidone in acute and long-term therapy of schizophrenia - a clinical profile. Progr Neuro-Psychoph 2004;28:15-23
25. Love RC, Nelson MW. Pharmacology and clinical experience with risperidone. Expert Opin Pharmacother 2000;1:1441-53
26. Tarsy D, Baldessarini Rj, Tarazi FI. Effects of newer antipsychotics, on extrapyramidal function. CNS Drugs 2002;16:23-45
27. Gaszner P, Makkos Z. Clozapine maintenance therapy in schizophrenia. Progr Neuro-Psychoph 2004;28:465-9
28. Raggi MA, Mandrioli R, Pucci V, Sabbioni C. Advances in therapeutic drug monitoring of atypical antipsychotic drugs. Med Chem Rev 2004;1:299-316
29. Stahl SM. Dopamine system stabilizers, Aripiprazole, and the next generation of antipsychotics, part 1, "Goldilocks" actions at dopamine receptors. J Clin Psychiat 2001;62:841-2
30. Davies MA, Sheffler DJ, Roth BL. Aripiprazole: a novel atypical antipsychotic drug with a uniquely robust pharmacology. CNS Drug Rev 2004;10:317-36
31. Swainston HT Perry CM. Aripiprazole. A review of its use in schizophrenia and schizoaftective disorder. Drugs 2004;64:1715-36
32. Stahl SM, Shayegan DK. The psychopharmacology of ziprasidone: receptor-binding properties and real-world psychiatric practice. J Clin Psychiat 2003;64(Suppl 19):6-12
33. Taylor D. Ziprasidone in the management of schizophrenia: the QT interval issue in context. CNS Drugs 2003;17:423-30
34. Racagni G, Canonico PL, Ravizza L, et al. Consensus on the use of substituted benzamides in psychiatric patients. Neuropsychobiology 2004;50:134-43
35. Pani L, Gessa GL. The substituted benzamides and their clinical potential on dysthymia and on the negative symptoms of schizophrenia. Mol Psychiatr 2002;7:247-53
36. Thomson Centerwatch website, 2007. Availible from: URL: http://www.centerwatch.com/patient/drugs/area17.html
37. Lindstroem E, Levander S. Sertindole: efficacy and safety in schizophrenia. Expert Opin Pharmacother 2006;7:1825-34
38. Serdolect website, 2006. Available from: http://www.serdolect.com/ content/downloadarea/pdf/serdolect_monograph.pdf
39. Revill P, Serradell N, Bolos J. Paliperidone. Antipsychotic agent, treatment of bipolar disorder, dual dopamine D2/5-HT2A receptor antagonist. Drug Future 2006;31:579-84
40. Owen RT. Extended-release patiperidone: efficacy, safety and tolerability profile of a new atypical antipsychotic. Drugs Today 2007;43:249-58
41. Yang LPH, Plosker GL. Paliperidone extended release. CNS Drugs 2007;21:417-25
42. FDA website, 2007. Available from: URL: http://www.fda.gov/cder/foi/ label/2006/021999lbl.pdf
43. Auclair AL, Galinier A, Besnard J, et al. Putative antipsychotics with pronounced agonism at serotonin 5-HT1A and partial agonist activity at dopamine D2 receptors disrupt basal PPI of the startle reflex in rats. Psychopharmacology 2007;193:45-54
44. Wadenberg M-LG. Bifeprunox: a novel antipsychotic agent with partial agonist properties at dopamine D2 and serotonin 5-HT1A receptors. Future Neurol 2007;2:153-65
45. Wyeth Pharmaceuticals, Inc. website press release. Available from: URL: http://www.wyeth.com/news?nav=display&pnavTo=/wyeth_html/home/news/ pressreleases/2007/1186749065400.html
46. Fleming K, Potkin SG, Binneman B, et al. Asenapine cognitive function effects in acute schizophrenia: a placebo- and risperidone-controlled trial. NCDEU, Boca Raton, USA: 47th Annual Meeting, 2007; Session 1-72
47. Potkin SG. Asenapine safety and tolerability during acute schizophrenia: a placebo- and risperidone-controlled trial. American Psychiatric Association, Toronto, Canada. 159th Annual Meeting, 2006; NR420
48. Hirschfeld RM. Asenapine in acute mania: a randomized, double blind, placebo- and olanzapine-controlled trial (ARES 7501005). San Diego, USA: American Psychiatric Association, 160th Annual Meeting, 2007; NR.333
49. Andree B, Halldin C, Vrijmoed-De Vries M, Farde L. Central 5-HT2A and D2 dopamine receptor occupancy after sublingual administration of ORG 5222 in healthy men. Psychopharmacology 1997;131:339-45
50. Dainippon Sumitomo Pharma Co. website, 2007. Available from: URL: http://www.ds-pharma.co.jp/english/rd/pdf)prof_20070730e.pdf
51. Keppel Hesselink JM. Iloperidone. IDrugs 2002;5:84-90
52. Titan Pharmaceuticals, Inc. website press release, 2004. Available from: URL: http://www.titanpharm.com/press/Zomaril_Japan.html
53. Titan Pharmaceuticals, Inc. website press release, 2004. Available from: URL: http//www.titanpharm.com/press/IloperidoneLicense.htm
54. Vanda Pharmacueticals, Inc. website, 2007. Available from: URL: http://www.vandapharmaceuticals.com/development.html
55. Caccia S. Biotransformation of post-clozapine antipsychotics. Clin Pharmacokinet 2000;38:393-414
56. Mucke HA, Castanet J. Iloperidone. Drug Future 2000;25:29-40
57. Strupczewski JT. Bordeau KJ, Chiang Y, et al. 3-(Aryloxy)alkyllpiperidinyl- 1,2-benzisoxazoles as D2/5-HT2 antagonists with potential atypical antipsychotic activity: antipsychotic profile of floperidone (HP 873). J Med Chem 1995;38:1119-31
58. Szewczak MR, Corbett R, Rush DK et al. The pharmacological profile of iloperidone, a novel atypical antipsychotic agent. J Pharmacol Exp Ther 1995;274: 1404-13
59. Kongsamut S, Roehr JE, Can J, et al. Iloperidone binding to human and rat dopamine and 5-HT receptors. Eur J Pharmacol 1996;317:417-23
60. Kalkman HO, Subramanian N, Hoyer D. Extended radioligand binding profile of iloperidone: a broad spectrum dopamine/serotonin/norepinephrine receptor antagonist for the management of psychotic disorders. Neuropsychopharmacology 2001;25:904-14
61. 1A receptors. Life Sci 2003;73:1151-9
62. 2C-adrenoceptor blockade by dozapine and other antipsychotic drugs. Eur J Pharmacol 2003;462:33-40
63. 2 receptor antagonist activity. J Pharmacol Exp Ther 1996;278:913-20
64. Barr AM, Powell SB, Markou A, Geyer MA. Iloperidone reduces sensorimotor gating deficits in pharmacological models, but not a developmental model of disrupted prepulse inhibition in rats. Neuropharmacology 2006;51:457-65
65. Corbett R, Griffiths L, Shipley JE, et al. Iloperidone: preclinical profile and early clinical evaluation. CNS Drug Rev 1997;3:120-47
66. Corbett R, Hartman H, Kerman LL, et al. Effects of atypical antipsychotic agents on social behavior in rodents. Pharmacol Biochem. 1993;459-17
67. Gemperle AY, McAllisteR KH, Olpe HR. Differential effects of iloperidone, clozapine, and haloperidol on working memory of rats in the delayed non-matching-to-position paradigm. Psychopharmacology 2003;169:354-64
68. Jain KK. An assessment of iloperidone for the treatment of schizophrenia. Expert Opin Investig Drugs 2000;9:2935-43
69. Sainati M, Hubbard JW, Chi E, et al. Safety, tolerability, and effect of food on the pharmacokinetics of iloperidone (HP 873), a potential atypical antipsychotic. J. Clin Pharmacol 1995;35:713-20
70. Fairweather DB, Young E, Zaninelli R. Iloperidone is effective and well tolerated in the long term treatment of schizophrenia and schizoaffective disorder. Eur Neuropsychopharm 2001;12(Suppl 3 P.2.054)
71. Vanda Pharmaceuticals Inc. website press release, 2006. Available from: URL: http://phx.corporate-ir.net/phoenix.zhtml?c=196233&p= irol-newsArticle_Print&ID=939941&highlight=
72. El-Bizri H, Fairweather DB, Guven A, Zaninelli R. Efficacy and tolerability of iloperidone in elderly patients with psychotic and behavioral symptoms associated with dementia. Eur Neuropsychopharm 2001;12(Suppl 3 P.2.055)
73. Baroldi P, Wolfgang C. A Pharmacokinetic (PK)-Pharmacodynamic (PD) relationship exist for efficacy of iloperidone: a novel investigation atypical antipsychotic agent. San Diego, USA. American Psychiatric Association, 160th Annual Meeting, 2007; NR507
74. Mutlib AE, Strupczewski JT, Chesson SM. Application of hyphenated LC/NMR and LC/MS techniques in rapid identification of in vitro and in vivo metabolites of iloperidone. Drug Metab Dispos 1995;23:951-64
75. Caccia S. New antipsychotic agents for schizophrenia: pharmacokinetics and metabolism update. Curr Opin Invest Drugs 2002;3:1073-80
76. Mutlib AE, Klein JT. Application of liquid chromatography/mass spectrometry in accelerating the identification of human liver cytochrome P450 isoforms involved in the metabolism of iloperidone. J Pharmacol Exp Ther 1998;286:1285-93
77. Chesson SM, Hsu RS, Dileo EM, Strupczewski JT. Pharmacokinetics of HP 873, a potential atypical antipsychotic, in rats and dogs abstract. Pharmacologist 1991;33:177-82
78. Subramanian N, Kalkman HO. Receptor profile of P88-8991 and P95-12113, metabolites of the novel antipsychotic iloperidone. Progr Neuro-Psychoph 2002;26:553-60
79. Wolfgang C. Genotyping facilitates individualized prediction of pharmacokinetic response to iloperidone in extensive and Poor CYP2D6 metabolizers. San Diego, USA. American Psychiatric Association, 160th Annual Meeting, 2007; NR508
80. Sedek G, Wolfgang C. Iloperidone is well tolerated by subjects with renal or hepatic impairment in single-dose clinical pharmacokinetic studies. San Diego, USA: American Psychiatric Association, 160th Annual Meeting, 2007; NR476
81. McCollough K, Wolfgang C. Iloperidone, a novel atypical antipsychotic, is associated with improvement, or no change, in akathisia symptoms. San Diego, USA: American Psychiatric Association, 160th Annual Meeting, 2007; NR475
82. Titan Pharmaceuticals, Inc. website press release, 2002. Available from: URL: http://www.titanpharm.com/press/Iloperidone_EKG.html
83. Yerrabolu M, Prabhudesai S, Tawam M, et al. Effect of risperidone on QT interval and QT dispersion in the elderly. Heart Dis 2000;2:10-2
84. Albers LJ, Ozdemir V. Pharmacogenomic-guided rational therapeutic drug monitoring: conceptual framework and application platforms for atypical antipsychotics. Curr Med Chem 2004;11:297-312
85. Mutlib AE, Strupczewski JT. Picogram determination of iloperidone in human plasma by solid-phase extraction and by high-performance liquid chromatography-selected-ion monitoring electrospray mass spectrometry. J Chromatogr B 1995;669:237-46
86. Kane J, Honigfeld G, Singer J, Meltzer H. Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiat 1988;45:798-6
87. Titan Pharmaceuticals, Inc. website, 2006. Available from: URL: http://www.titanpharm.com/pdf/VANDA-Iloperidone-Prospectus.pdf
88. Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005;353:1209-23