Iloperidone. Antipsychotic dopamine D2 antagonist 5-HT(2A) antagonist

Drugs of the Future

Volumn 25, Issue 1, 2000, Pages 29-40

  Mucke, Hermann A M ^a   Castaner J ^b  

^a Prous Science ^*  (Austria)

^b PROUS SCIENCE   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

1 (3 CHLORO 4 CYCLOHEXYLPHENYL) 3 (HEXAHYDRO 1 AZEPINYL)PROPENE; 1,2,3,6 TETRAHYDRO 4 PHENYL 1 [(3 PHENYL 3 CYCLOHEXEN 1 YL)METHYL]PYRIDINE; 2 [[1 (7 CHLORO 4 QUINOLINYL) 5 (2,6 DIMETHOXYPHENYL) 3 PYRAZOLYL]CARBONYLAMINO] 2 ADAMANTANECARBOXYLIC ACID; 4 (4 FLUOROPHENYL) 1,2,3,6 TETRAHYDRO 1 [4 (1,2,4 TRIAZOL 1 YL)BUTYL]PYRIDINE; 6 QUINOXALINECARBOXYLIC ACID PIPERIDIDE; AMISULPRIDE; AMPEROZIDE; ARIPIPRAZOLE; BELAPERIDONE; BIFEPRUNOX; BLONANSERIN; CEE 03 310; CHLORPROMAZINE; CLOZAPINE; EPLIVANSERIN; HALOPERIDOL; ILOPERIDONE; MAZAPERTINE; NEUROLEPTIC AGENT; OLANZAPINE; ORG 5522; OSANETANT; PEROSPIRONE; RISPERIDONE; SONEPIPRAZOLE; UNCLASSIFIED DRUG; ZIPRASIDONE;

ARTICLE; BINDING AFFINITY; BINDING SITE; CLINICAL TRIAL; DRUG MECHANISM; DRUG METABOLISM; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; NEUROTOXICITY; RECEPTOR BINDING; SCHIZOPHRENIA;

EID: 0343986371     PISSN: 03778282     EISSN: None     Source Type: Journal    
DOI: 10.1358/dof.2000.025.01.563065     Document Type: Article

References (65)

1. Strupczewski, J.T., Gardner, B.A., Allen, R.C. (Hoechst-Roussel Pharmaceuticals). 3-(4-Piperidyl)-1,2-benzisoxazoles. US 4355037.
2. 2 antagonists with potential atypical antipsychotic activity: Antipsychotic profile of iloperidone (HP 873). J Med Chem 1995, 38: 1119-31.
3. Strupczewski, J.T., Helsley, G.C., Chiang, Y., Bordeau, K.J. (Hoechst-Roussel Pharmaceuticals, Inc.). N-(Aryloxyalkyl)heteroarylpiperidines and-heteroarylpiperazines, a process for their preparation and their use as medicaments. EP 402644, JP 91063263.
4. Strupczewski, J.T., Helsley, G.C., Glamkowski, E.J., Chiang, Y., Bordeau, K.J., Nemoto, P.A., Tegeler, J.J. (Hoechst Marion Roussel, Inc.). Heteroarylpiperidines, pyrrolidines and piperazines and their use as antipsychotics and analgetics. EP 542136, EP 612318, EP 730452, JP 95501055, JP 97511215, US 5364866, US 5776963, WO 9309102, WO 9511680.
5. Seeman P. Dopamine receptors and the dopamine hypothesis of schizophrenia. Synapse 1987, 1: 133-52.
6. 2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects. Arch Gen Psychiatry 1992, 49: 538-44.
7. 6 serotonin receptors may reflect psychoactive profile. Mol Med 1995, 1: 398-406.
8. Meltzer, H.Y., Nash, J.F. Effects of antipsychotic drugs on serotonin receptors. Pharmacol Rev 1991, 43: 587-604.
9. 2 receptor blocking agent. Clin Ther Res 1986, 40: 492-9.
10. Roth, B.L., Craigo, S.C., Choudhary, M.S., Uluer, A., Monsma, F.J. Jr., Shen, Y., Meltzer, H.Y., Sibley, D.R. Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J Pharmacol Exp Ther 1994, 268: 1403-10.
11. 2A receptor blockade. J Pharmacol Exp Ther 1999, 288: 590-6.
12. Andreasen, N.C., Flaum, M., Swayze, V.W., Tyrell, G., Arndt, S. Positive and negative symptoms in schizophrenia: A critical reappraisal. Arch Gen Psychiatry 1990, 47: 615-21.
13. Gelder, Y.G. Thymosthenic agents: A novel approach in the treatment of schizophrenia. Br J Psychiatry 1989, 155 (Suppl. 5): 33-6.
14. Kinon, B.J., Lieberman, J.A. Mechanisms of action of antipsychotic drugs - A critical analysis. Psychopharmacology 1996, 124: 2-34.
15. 2-adrenoceptor blockade. Science 1999, 286: 105-7.
16. Strupczewski, J.T., Allen, R.C., Gardner, B.A., Schmid, B.L., Stache, U., Glamkowski, E.J., Jones, M.C., Ellis, D.B., Huger, P.P., Dunn, R.W. Synthesis and neuroleptic activity of 3-(1-substituted-4-piperidinyl)-1,2-benzisoxazoles. J Med Chem 1985, 28: 761-9.
17. 2 receptor antagonist activity. Soc Neurosci Abst 1990, 16: Abst 109.12.
18. Szewczak, M.R., Dunn, R.W., Corbett, R., Geyer, H.M., Rush, D.K., Wilker, J.C., Strupczewski, J.T., Helsley, G.C., Cornfeldt, M. The in vivo pharmacology of the novel antipsychotic HP 873. Soc Neurosci Abst 1990 16: Abst 109.13.
19. 2 antagonist with the profile of a potential atypical antipsychotic. 200th ACS Natl Meet (Aug 26-31, Washington DC) 1990, Abst MEDI 2.
20. 2 receptor antagonist activity. J Pharmacol Exp Ther 1996, 278: 913-20.
21. 2) receptors in the rat brain. Brain Res 1989, 487: 288-98.
22. Hartman, H., Cai, J., Kerman, L.L., Weissensee, P., Roehr, J.E., Tang, L., Sandrasagra, A., Kongsamut, S. Iloperidone binding to human dopamine receptors: Comparison with other antipsychotics. Soc Neurosci Abst 1995, 21 (Part 1): Abst 252.16.
23. Kongsamut, S., Roehr, J.E., Cai, J., Hartman, H.B., Weissensee, P., Kerman, L.L., Tang, L., Sandrasagra, A. Iloperidone binding to human and rat dopamine and 5-HT receptors. Eur J Pharmacol 1996, 317: 417-23.
24. Strupczewski, J.T., Bordeau, K.J., Dunn, R.W., Hartman, H.B., Roehr, J.E., Conway, P.G. Antipsychotic activity of 1H-indazol-3-yl piperidine and piperazine analogs of the potential atypical antipsychotic HP 873. 203rd ACS Natl Meet (April 5-10, San Francisco) 1992, Abst MEDI 87.
25. Strupczewski, J.T., Bordeau, K.J., Glamkowski, E.J., Fink, D.M., Bregna, D.E., Corbett, R., Hartman, H.B., Roehr, J.E., Szewczak, M.R., Woods, A.T. Antipsychotic activity of 1,2-benzisothiazole analogs of the potential atypical antipsychotic iloperidone (HP 873). 210th ACS Natl Meet (Aug 20-24, Chicago) 1995, Abst MEDI 138.
26. Chesson, S.M., Hsu, R.S., DiLeo, E.M., Strupczewski, J.T. Pharmacokinetics of HP 873, a potential atypical antipsychotic, in rats and dogs. Pharmacologist 1991, 33 (3): Abst 202.
27. Mutlib, A.E., Strupczewski, J.T., Chesson, S.M. 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.
28. Mutlib, A.E., Klein, J.T. 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.
29. Mutlib, A.E., Strupczewski, J.T. 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 - Biomed Appl 1995, 669: 237-46.
30. Milstein, V., Small, J.G., Brecher, M.B., Kellams, J.J., Small, I.F. Pharmaco-EEG studies of single doses of an atypical neuroleptic iloperidone, compared with chlorpromazine and placebo in schizophrenic patients. Biol Psychiatry 1994, 35 (9): Abst 204.
31. Sainati, S.M., Hubbard, J.W., Chi, E., Grasing, K., Brecher, M.B. Safety, tolerability, and effect of food on the pharmacokinetics of iloperidone (HP 873), a potential atypical antipsychotic [published erratum appears in J Clin Pharmacol 1996, 36 (1): 92]. J Clin Pharmacol 1995, 35: 713-20.
32. Corbett, R., Griffiths, L., Shipley, J.E. et al. Iloperidone: Preclinical profile and early clinical evaluation. CNS Drug Rev 1997, 3: 120-47.
33. Davidson, M., Brecher, M.B., Kahn, R., Stern, R., Macaluso, J. Iloperidone (HP 873): A study of safety and tolerance in schizophrenic inpatients. Psychopharmacol Bull 1994, 30: 664.
34. Sha, X., Shukla, U., Dix, R., Shipley, J.E., Chi, E. Safety and steady-state pharmacokinetics of a new oral antipsychotic agent, iloperidone, administered to schizophrenic patients. Pharm Res 1996, 13 (9, Suppl.): Abst CS 3001.
35. Borison, R.L., Huff, F.J., Griffiths, L., Ramaswamy, R., Shipley, J.E. Efficacy of 4 mg/day and 8 mg/day iloperidone (HP 873) administered to schizophrenic patients for 42 days. Psychopharmacol Bull 1996, 32: 416.
36. Cutler, N.R., Shipley, J.E., Varaklis, J., Hourani, J., Jhee, S.S., Sramek, J.J. A bridging study of iloperidone in schizophrenic inpatients. Psychopharmacol Bull 1996, 32: 428.
37. Phase III Zomaril trial yields encouraging preliminary results. DailyDrugNews.com (Daily Essentials) Dec 6, 1999.
38. Corbett, R., Hartman, H., Kerman, L.L., Woods, A.T., Strupczewski, J.T., Helsley, G.C., Conway, P.C., Dunn, R.W. Effects of atypical antipsychotic agents on social behavior in rodents. Pharmacol Biochem Behav 1993, 45: 9-17.
39. Szewczak, M.R., Corbett, R., Rush, D.K., Wilmot, C.A., Conway, P.G., Strupczewski, J.T., Cornfeldt, M. The pharmacological profile of iloperidone, a novel atypical antipsychotic agent. J Pharmacol Exp Ther 1995, 274: 1404-13.
40. i values. J Pharmacol Exp Ther 1989, 251: 238-46.
41. 2A receptors. Eur J Pharmacol 1994, 261: 285-94.
42. 2 receptor antagonist and potential new antipsychotic. 213th ACS Natl Meet (April 13-17, San Francisco) 1997, Abst MEDI 186.
43. 1A agonist properties: I. Receptorial and neurochemical profile in comparison with clozapine and haloperidol. J Pharmacol Exp Ther 1998, 286: 1341-55.
44. 1-adrenergic as compared to dopamine D2 receptors by novel antipsychotics. Eur Neuropsychopharmacol 1995, 5 (3): Abst P-4-12.
45. Bymaster, F.P., Calligaro, D.O., Falcone, J.F., Marsh, R.D., Moore, N.A., Tye, N.C., Seeman, P., Wong, D.T. Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology 1996, 14: 87-96.
46. 2 receptors, and an "atypical" antipsychotic profile in the rat. Br J Pharmacol 1995, 114 (Suppl.): Abst 156P.
47. 2A) receptors of 1-(benzoylpropyl)-4-(1-oxocycloalkyl-2-ethyl)-piperazines as cyclic butyrophenone derivatives. Chem Pharm Bull 1996, 44: 534-41.
48. 2A receptors by sertindole in the rat brain. J Psychiatry Neurosci 1998, 23: 157-62.
49. 2A receptor ligand. Naunyn-Schmied Arch Pharmacol 1996, 354: 205-9.
50. 4 receptors: A comparison to haloperidol, dozapine and ziprasidone. IBC 1st Int Symp Schizophrenia (May 8-9, Philadelphia) 1995.
51. 4 receptors. Br J Pharmacol 1996, 117: 1625-32.
52. Markstein, R., Gull, P., Rudeberg, C., Urwyler, S., Jaton, A.L., McAllister, K., Dixon, A.K., Hoyer, D. SDZ PSD 958, a novel D1 receptor antagonist with potential limbic selectivity. J Neural Transm 1996, 103: 261-76.
53. Campiani, G., Nacci, V., Bechelli, S. et al. New antipsychotic agents with serotonin and dopamine antagonist properties based on a pyrrolo[2,1-b][1,3]benzothiazepine structure. J Med Chem 1998, 41: 3763-72.
54. Reitz, A.B., Baxter, E.W., Bennett, D.J. et al. N-aryl-N′-Benzylpiperazines as potential antipsychotic agents. J Med Chem 1995, 38: 4211-22.
55. Scott, M.K., Baxter, E.W., Bennett, D.J. et al. Piperazinylalkyl heterocycles as potential antipsychotic agents. J Med Chem 1995, 38: 4198-210.
56. Seeger, T.F., Seymour, P.A., Schmidt, A.W. et al. Ziprasidone (CP-88,059): A new antipsychotic with combined dopamine and serotonin receptor antagonist activity. J Pharmacol Exp Ther 1995, 275: 101-13.
57. 2 receptor antagonist MDL-100907 as a putative atypical antipsychotic: Behavioral, electrophysiological and neurochemical studies. J Pharmacol Exp Ther 1993, 266: 684-91.
58. 2A antagonist with a favorable CNS safety profile. J Pharmacol Exp Ther 1996, 277: 968-81.
59. Ögren, S.O., Archer, T. Effects of typical and atypical antipsychotic drugs on two-way active avoidance. Relationship to DA receptor blocking profile. Psychopharmacology 1994, 114: 383-91.
60. 1 adrenoceptor antagonist (R)-(+)-2-amino-4-(4-fluorophenyl)-5-[1-[4-(4-fluorophenyl)-4-oxobutyl] pyrrolidin-3-yl]thiazole (NRA0045). J Pharmacol Exp Ther 1997, 282: 56-63.
61. Hrib, N.J., Jurcak, J.G., Bregna, D.E. et al. Structure-activity relationships of a series of novel (piperazinylbutyl)thiazolidinone antipsychotic agents related to 3-[4-[4-(6-fluorobenzo[b]thien-3-yl)-1-piperazinyl]butyl]-2,5,5-trimethyl-4- thiazolidinone maleate. J Med Chem 1996, 39: 4044-57.
62. 2A receptor antagonist, in rats. Br J Pharmacol 1997, 121: 515-25.
63. Lang, A., Soosaar, A., Koks, S., Volke, V., Bourin, M., Bradwejn, J., Vasar, E. Pharmacological comparison of antipsychotic drugs and σ-antagonists in rodents. Pharmacol Toxicol 1994, 75: 222-7.
64. Broekkamp, C.L., De Graaf, J.S., van Delft, A.M. Behavioural pharmacology of trans-5-chloro-2-methyl-2,3,3a, 12b-tetrahydro-1H-dibenz[2,3:6,7]oxepino-[4,5-c]pyrrolidine maleate, a compound interacting with dopaminergic and serotonergic receptors. Arzneim-Forsch Drug Res 1990, 40: 544-9.
65. 3 dopamine receptor antagonist activity and limbic selectivity. J Pharmacol Exp Ther 1997, 280: 73-82.