Iloperidone: Preclinical profile and early clinical evaluation

CNS Drug Reviews

Volumn 3, Issue 2, 1997, Pages 120-147

  Corbett, R ^a   Griffiths, L ^a   Shipley, J E ^a   Shukla, U ^a   Strupczewski, J T ^a   Szczepanik, A M ^a   Szewczak, M R ^a   Turk, D J ^a   Vargas, H M ^a   Kongsamut, S ^a   Allen, R C ^a   Bordeau, K J ^a   Brecher, M B ^a   Bregna, D ^a   Brooks, K M ^a   Brougham, L ^a   Cai, J ^a   Chesson, S M ^a   Chi, E ^a   Chiang, Y ^a   Conway, P G ^a   Cornfeldt, M L ^a   Cunningham, D M ^a   DiLeo, E M ^a   Dunn, R W ^a   Ellis, D B ^a   Effland, R C ^a   Folden Gellock, M ^a   Glamkowski, E J ^a   Gorman, A J ^a   Grasing, K ^a   Hanak, S ^a   Hartley, T ^a   Hartman, H B ^a   Helsley, G ^a   Hsu, R S ^a   Hubbard, J W ^a   Jackson, O T ^a   Kerman, L L ^a   Mutlib, A E ^a   Ramaswamy, R ^a   Ricker, L L ^a   Roehr, J E ^a   Rush, D K ^a   Sainati, S M ^a   Sandrasagra, A ^a   Stamer, S ^a   Tang, L ^a   Turcan, R ^a   Varaklis, J ^a   Weissensee, P ^a   Wilmot, C A ^a   Woods Kettelberger, A T ^a   Zumpano, L ^a   more..

^a SANOFI   (France)

Author keywords

Antipsychotics; HP 873; Iloperidone; Schizophrenia

Indexed keywords

ILOPERIDONE; NEUROLEPTIC AGENT;

ANIMAL TISSUE; DOPAMINE BRAIN LEVEL; DRUG RECEPTOR BINDING; DRUG USE; HUMAN; MEMORY; NONHUMAN; RAT; RECEPTOR AFFINITY; REVIEW; SCHIZOPHRENIA;

EID: 12644311274     PISSN: 1080563X     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1527-3458.1997.tb00320.x     Document Type: Review

References (93)

1. Andreasen NC, Flaum M, Swayze VW, Tyrrell G, Arndt S. Positive and negative symptoms in schizophrenia: A critical reappraisal. Arch Gen Psychiatry 1990;47:615-621.
2. 2 receptors in rat cerebral cortex. J Neurochem 1986;46:191-197.
3. Baldessarini RJ. Drugs and the treatment of psychiatric disorders. In: Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, and Gilman AG, eds. The Pharmacological Basis of Therapeutics, Ninth Edition. New York: McGraw Hill, 1996:399-430.
4. Baldessarini RJ, Tarsey D. Relationship of the actions of neuroleptic drugs to the pathophysiology of tardive dyskinesia. Int Rev Neurobiol 1979;21:1-44.
5. Baldessarini RJ, Frankenburg FR. Drug therapy: Clozapine. New Eng J Med 1991;324:746-754.
6. Baldessarini RJ, Hulston-Lyons D, Campbell A, Marsh E, Cohen BM. Do central antiadrenergic actions contribute to the atypical properties of clozapine? Br J Pharmacol (Suppl 17) 1992;160;12-16.
7. Barnes TR. A rating scale for drug-induced akathisia. Br J Psychiatr 1989;154:672-676.
8. Beasley CM, Tollefson G, Tran P, et al. Olanzapine versus placebo and haloperidol: Acute phase results of the North American double-blind olanzapine trial. Neuropsychopharmacology 1996;14:111-123.
9. 2 receptor blocking agent. Clin Ther Res 1986;40:492-499.
10. 2 antagonism: Clinical, extrapyramidal and neuroendocrine response in a preliminary study with risperidone (R64766). Human Psychopharmacol 1990;5:225-231.
11. Borison RL, Huff FJ, Varaklis J, Griffiths L, Ramaswamy R, Shipley J. Efficacy of 2 and 4 mg BID iloperidone (HP 873) administered to schizophrenic patients for 42 days. ACNP Abstr 1995;34:135.
12. Bunney BS, Grace AA. Acute and chronic haloperidol treatment: Comparison of effects on nigral dopaminergic cell activity. Life Sci 1978;23:1715-1728.
13. Carlsson AJ, Kehr W, Lindqvist M, Magnusson T, Atack CV. Regulation of monoamine metabolism in the central nervous system. Pharmacol Rev 1972;24:371-384.
14. Carlsson M, Carlsson A. Interactions between glutamatergic and monoaminergic systems within the basal ganglia - implications for schizophrenia and Parkinson's disease. Trends Neurol Sci 1990;13:272-276.
15. 2 antagonist risperidone (R64766) in the treatment of chronic psychosis. Schizophr Res 1989;2:411-415.
16. Chesson SM, Hsu RS, DiLeo EM, Strupczewski JT. Pharmacokinetics of HP 873, a potential atypical antipsychotic, in rats and dogs. Pharmacologist 1991;33:177.
17. Chiodo LA, Bunney BS. Possible mechanisms by which repeated clozapine administration differentially affects the activity of two subpopulations of midbrain dopamine neurons. J Neurosci 1985;5:2539-2544.
18. 2 dopamine receptor classification and its functional implications. Synapse 1987;1:347-388.
19. Claus A, Bollen J, DeCuyper H, et al. Risperidone vs. Haloperidol in the treatment of chronic schizophrenic inpatients: A multicenter double-blind comparative study. Acta Psychiatr Scand 1992;85:295-305.
20. Clow A, Theodorou A, Jenner P, Marsden CD. Changes in cerebral dopamine function induced by a year's administration of trifluoperazine or thioridazine and their subsequent withdrawal. In: Cattabeni F et al., eds. Long Term Effects of Neuroleptic. New York: Raven Press, 1980:353-340.
21. Cook L, Weidley E. Behavioral effects of some psychopharmacological agents. Ann NY Acad Sci 1957;66:740-752.
22. Corbett R. Clozapine but not haloperidol antagonizes an MK-801 discriminative stimulus cue. Pharmacol Biochem Behav 1995;51:561-564.
23. Corbett R, Dunn RW. Effects of 5,7-dichlorokynurenic acid on conflict, social interaction and elevated plus maze behaviors. Neuropharmacology 1993;32:461-466.
24. Corbett R, Hartman H, Kerman LL, et al. Effects of atypical antipsychotic agents on social behavior in rodents. Pharmacol Biochem Behav 1993;45:9-17.
25. Corbett R, Camacho F, Woods AT, et al. Antipsychotic agents antagonize non-competitive N-methyl-d-aspartate antagonist-induced behaviors. Psychopharmacology 1995;120:67-74.
26. Costall B, Naylor RJ, Cannon JG, Lee T. Differentiation of the dopamine mechanisms mediating stereotyped behaviour and hyperactivity in the nucleus accumbens and caudate-putamen. J Pharm Pharmacol 1977, 29:337-342.
27. Costall B, Eniojukan JF, Naylor RJ. The mesolimbic nucleus accumbens is critically involved with the mediation of the motor inhibitory and facilitory effects of dopamine agonists on mouse spontaneous climbing behavior. Eur J Pharmacol 1983;96:201-210.
28. Costall B, Naylor RJ. Behavioral interactions between 5-hydroxytryptophan, neuroleptic agents, and 5-HT receptor antagonists in modifying rodent responding to aversive situations. Br J Pharmacol 1995;116:2989-2999.
29. Creese I, Burt DR, Snyder SH. Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 1976;192:481-483.
30. Davis KL, Kahn RS, Ko G, Davidson M. Dopamine in schizophrenia: A review and reconceptualization. Am J Psychiatry 1991;148:1474-1486.
31. DeMaio D. Clozapine, a novel major tranquilizer. Arzneim Forsch 1972;22:919-923.
32. 1A receptor agonists and NMDA receptor antagonists in the social interaction test and the elevated plus maze. Eur J Pharmacol 1989;169: 1-10.
33. 6 serotonin receptors may reflect psychoactive profile. Mol Med 1995;1:398-406.
34. Grace AA, Bunney BS. Induction of depolarization block in midbrain dopamine neurons by repeated administration of haloperidol: Analysis using in vivo intracellular recording. J Pharmacol Exp Ther 1986;238:1092-1100.
35. Guy, W. ECDEU Assessment Manual for Psychopharmacology. Washington DC: US Department of Health Education and Welfare, 1976:534-537.
36. Hoyberg OJ, Remvig FC, Lingjaerde O, Sloth-Nielsen M, Salvesen I. Risperidone versus perphenazine in the treatment of chronic schizophrenic patients with acute exacerbations. Acta Psychiatr Scand 1993;88:395-402.
37. Iversen SD. Is it possible to model psychotic states in animals? J Psychopharmacol 1987;1:154-176.
38. Jann MW. Buspirone: An update on a unique anxiolytic agent. Pharmacotherapy 1988;8:100-116.
39. 2 properties. J Pharmacol Exp Ther 1988;244:685-693.
40. Janssen PAJ, Awouters FHL. Is it possible to predict clinical effects of neuroleptics from animal data? Arzneim Forsch/Drug Res 1994;44:269-277.
41. Javitt JDC, Zukin SR. Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry 1991;148:1301-1308.
42. Kane JM. Treatment of schizophrenia. Schizophr Bull 1987;13:133-156.
43. Kane JM, Honigfeld G, Singer J, Meltzer H, the Clozaril Collaborative Study Group. Clozapine for the treatment-resistant schizophrenic. Arch Gen Psychiatry 1988;45:789-796.
44. Kay SR, Fiszbein A, Opler LA. Positive and Negative Scale (PANSS) Manual. Toronto: Multi-Health Systems Inc. 1990.
45. Koek W, Colpaert FC, Woods JH, Kamenka JM. The phencyclidine (PCP) analog N-[1[2-benzo(B)thiophenyl-cyclohexyl]piperidine shares cocaine-like but not other characteristic behavioral effects with PCP, ketamine and MK-801. J Pharmacol Exp Ther 1989;250:1019-1017.
46. Kongsamut S, Roehr JE, Cai J, et al. Iloperidone binding to human and rat dopamine and serotonin receptors. Eur J Pharmacol 1996;317:417-423.
47. Kuribara H, Tadokoro S. Correlation between antiavoidance activities of antipsychotic drugs in rats and daily clinical doses. Pharmacol Biochem Behav 1981;14:181-192.
48. 2) receptor numbers in the rat brain. Psychiatry Res 1984;12:277-285.
49. Leysen JE, Gommeren W, Eens A, et al. Biochemical profile of risperidone, a new antipsychotic. J Pharmacol Exp Ther 1988;247:661-670.
50. Leysen JE, Janssen PMF, Schotte A, Luyten WHML, Megens AAHP. Interaction of antipsychotic drugs with neurotransmitter receptor sites in vitro and in vivo in relation to pharmacological and clinical role of 5-HT2 receptors. Psychopharmacology 1993; 112: S40.
51. Losonczy MF, Davidson M, Davis KL. The dopamine hypothesis of schizophrenia. In: Meltzer HY, ed. Psychopharmacohgy: The Third Generation of Progress. New York: Raven Press, 1987:715-726.
52. Lucki I, Nobler MS, Frazer A. Differential actions of serotonin antagonists on two behavioral models of serotonin receptor activation in the rat. J Pharmacol Exp Ther 1984;228:133-139.
53. Lucki I, Minugh-Purvis N. Serotonin-induced head shaking behavior in rats does not involve receptors in the frontal cortex. Brain Res 1987;420:403-406.
54. Meltzer HY. Relevance of dopamine autoreceptors for psychiatry: Preclinical and clinical studies. Schizophr Bull 1980;6:456-475.
55. Meltzer HY. Clinical studies on the mechanism of action of clozapine: The dopamine-serotonin hypothesis of schizophrenia. Psychopharmacology 1989;99:S18-S27.
56. Meltzer HY, Bastani B, Young Kwon K, Ramirez LF, Burnett S, Sharpe J. A prospective study of clozapine in treatment-resistant schizophrenic patients. Psychopharmacology 1989;99:568-572.
57. Meltzer HY, Burnett S, Bastani B, Ramirez LF. Effects of six months of clozapine treatment on the quality of life of chronic schizophrenic patients. Hosp Commun Psychiatry 1990;41:892-897.
58. Meltzer HY. Clozapine: Mechanism of action in relation to its clinical advantages. In: Kales A, Stefanos GN, Talbott JA, eds. Recent Advances in Schizophrenia. Heidelberg: Springer-Verlag, 1990:237-246.
59. Meilzer HY. Pharmacological treatment of negative symptoms. In: Greden JF, Tandom R, eds. Negative Schizophrenic Symptoms: Pathology and Clinical Implications. Washington: American Psychiatric Press Inc. 1991:215-231.
60. Meltzer HY. The importance of serotonin-dopamine interactions in the action of clozapine. Br J Psychiatry (Suppl 17) 1992;160:22-29.
61. Min SK, Rhee CS, Kim CE, Kang DY. Risperidone versus haloperidol in the treatment of chronic schizophrenic patients: A parallel group double-blind comparative trial. Yonsei Med J 1993;34:179-190.
62. Moore NA, Tye NC, Axton MS, Risius FC. The behavioral pharmacology of olanzapine, a novel "atypical" antipsychotic agent. J Pharmacol Exp Ther 1992;262:545-551.
63. Moore NA, Rees G, Sanger G, Tye NC. Effects of olanzapine and other antipsychotic agents on responding maintained by a conflict schedule. Behav Pharmacol 1994;5:196-202.
64. Moore NC, Gershon S. Which atypical antipsychotics are identified by screening tests? Clin Neuropharmacol 1989;12:167-184.
65. Muller P, Seeman P. Dopaminergic supersensitivity after neuroleptics: Time course and specificity. Psychopharmacology 1978, 60:1-11.
66. 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: Biomed Appl 1995;669:237.
67. 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 Disp 1995;23:951.
68. 2 antagonists. Drug Dev Res 1983;3:123-135.
69. O'Dell SJ, La Hoste GJ, Widmark CB, Shapiro RM, Putkin SG, Marshall JF. Chronic treatment with clozapine or haloperidol differentially regulates dopamine and serotonin receptors in rat brain. Synapse 1990;6:146-153.
70. Overall JE, Gorham DR. The brief psychiatric rating scale. Psychol Rep 1962;10:799-812.
71. Peroutka SJ, Lebovitz RM, Snyder SH. Two distinct central serotonin receptors with different physiological functions. Science 1978;212:827-829.
72. Rao ML, Muller HJ. Biochemical findings of negative symptoms in schizophrenia and their putative relevance to pharmacologic treatment. Neuropsychobiology 1994;30:160-164.
73. Regier DA, Boyd JH, Burk JD Jr, et al. One month prevalence of mental disorders in the US: Based on five epidemiologic catchment area (ECA) sites. Arch Gen Psychiatry 1988;45:977-986.
74. Roth BL, Craigo SC, Choudhary MS, et al. Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J Pharmacol Exp Ther 1994;268:1403-1410.
75. 2 receptor function in the rat. Biochem Pharmacol 1985;34:2755-2763.
76. Sainati SM, Hubbard JH, Chi E, Grasing K, Brecher M. Safety, tolerability, and effect of food on the pharmacokinetics of iloperidone (HP 873), a potential atypical antipsychotic. J Clin Pharmacol 1995;35:713-720.
77. Schotte A, Janssen PFM, Megens AAHP, Leysen JE. Occupancy of central neurotransmitter receptors by risperidone, clozapine, and haloperidol, measured ex vivo by quantitative autoradiography. Brain Res 1993;631:191-202.
78. Shopsin B, Klein H, Aaronsom M, Collora M. Clozapine, chlorpromazine, and placebo in newly hospitalized acutely schizophrenic patients. Arch Gen Psychiatry 1979;36:657-664.
79. Sidman M. Avoidance conditioning with brief shock and no exteroceptive warning signal. Science 1953;118:157-158.
80. Simpson GM, Angus JW. A rating scale for extrapyramidal side effects. Acta Psychiatr Scand Suppl 1970;212:11-19.
81. Sovner R, Parnell-Sovner N. Use of buspirone in the treatment of schizophrenia. J Clin Psychopharmacol 1989:9: 61-62.
82. 1 agonist dihydrexidine releases acetylcholine and improves cognition in rats. Ann NY Acad Sci 1996;777:427-430.
83. 2 receptors. J Pharmacol Exp Ther 1993;266:1374-1384.
84. 2 antagonists with potential atypical antipsychotic activity: Antipsychotic profile of iloperidone (HP 873). J Med Chem 1995;38:1119-1131.
85. 2 receptor antagonist activity. J Pharmacol Exp Ther 1996;278:913-920.
86. Szewcak MR, Corbett R, Rush DK, et al. The pharmacological profile of iloperidone, a novel atypical antipsychotic agent. J Pharmacol Exp Ther 1995;274:1404-1413.
87. 2C serotonin receptors. Nature 1995;374:542-546.
88. Umbricht D, Kane JM. Medical complications of new antipsychotic drugs. Schizophr Bull 1996;22:475-483.
89. 1 adrenoceptor subtypes in the pressor response to sympathetic nerve stimulation in the pithed rat. J Pharmacol Exp Ther 1994;271:748-754.
90. Walters JR, Roth RH. Dopaminergic neurons: An in vivo system for measuring drug interactions with presynaptic receptors. Naunyn-Schmiedeberg's Arch Pharmacol 1976;274:5-14.
91. Weiss JM, Kilts CD. Animal models of depression and schizophrenia. In: Schatzberg A, Nemeroff CB, eds. Textbook of Psychopharmacology. New York: The American Psychiatric Press, 1995:81-125.
92. Westerink BHC. The effects of drugs on dopamine biosynthesis and metabolism. In: Horn AS, Korf J, Westerink BHS, eds. Neurobiology of Dopamine. London: Academic Press, 1979:251-290.
93. 2) receptors in the rat brain. Brain Res 1989;487:288-298.