Pimavanserin, a serotonin 2A receptor inverse agonist, for the treatment of Parkinson's disease psychosis

Neuropsychopharmacology

Volumn 35, Issue 4, 2010, Pages 881-892

  Meltzer, Herbert Y ^a   Mills, Roger ^b   Revell, Stephen ^b   Williams, Hilde ^b   Johnson, Ann ^b   Bahr, Daun ^b   Friedman, Joseph H ^c  

^a Psychiatric Hospital at Vanderbilt   (United States)

^b ACADIA PHARMACEUTICALS INC   (United States)

^c BROWN UNIVERSITY   (United States)

Author keywords

Delusions; Hallucinations; Motor symptoms; Parkinson's disease; Pimavanserin (ACP 103)

Indexed keywords

CLOZAPINE; DOPAMINE RECEPTOR STIMULATING AGENT; LEVODOPA; PIMAVANSERIN; PLACEBO; QUETIAPINE; SEROTONIN 2A RECEPTOR;

ADULT; AGED; ARTICLE; ASTHENIA; BACKACHE; BALANCE DISORDER; CLINICAL ARTICLE; CLINICAL TRIAL; COGNITIVE DEFECT; CONFUSION; CONNECTIVE TISSUE DISEASE; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DEPRESSION; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG TOLERABILITY; EAR DISEASE; FALLING; FATIGUE; FEMALE; HALLUCINATION; HEADACHE; HUMAN; HYPOTENSION; INJURY; INNER EAR DISEASE; LEUKOCYTE COUNT; MALE; MENTAL DISEASE; MOTOR DYSFUNCTION; MOTOR PERFORMANCE; MULTICENTER STUDY; MUSCULOSKELETAL DISEASE; NEUROLOGIC DISEASE; ORTHOSTATIC HYPOTENSION; PARKINSON DISEASE; PERIPHERAL EDEMA; PRIORITY JOURNAL; PSYCHOSIS; RANDOMIZED CONTROLLED TRIAL; SCORING SYSTEM; SEDATION; SIDE EFFECT; SOMNOLENCE; UREA BLOOD LEVEL; VASCULAR DISEASE; VERTIGO;

AGED; ANALYSIS OF VARIANCE; DOUBLE-BLIND METHOD; FEMALE; FOLLOW-UP STUDIES; HUMANS; MALE; MOTOR ACTIVITY; PARKINSON DISEASE; PIPERIDINES; PSYCHIATRIC STATUS RATING SCALES; PSYCHOTIC DISORDERS; RECEPTOR, SEROTONIN, 5-HT2A; SEROTONIN AGONISTS; SEVERITY OF ILLNESS INDEX; UREA;

EID: 76749104144     PISSN: 0893133X     EISSN: None     Source Type: Journal    
DOI: 10.1038/npp.2009.176     Document Type: Article

References (71)

1. Andreasen NC (1984). Scale for Assessment of Positive Symptoms (SAPS). Department of Psychiatry, University of Iowa: Iowa City, IA.
2. Arana GW (2000). An overview of side effects caused by typical antipsychotics. J Clin Psychiatry 61(Suppl 8): 5-11.
3. Assal F, Alarcón M, Solomon EC, Masterman D, Geschwind DH, Cummings JL (2004). Association of the serotonin transporter and receptor gene polymorphisms in neuropsychiatric symptoms in Alzheimer disease. Arch Neurol 61: 1249-1253.
4. Ballard C, Hanney ML, Theodoulou M, Douglas S, McShane R, Kossakowski K et al (2009). The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial. Lancet Neurol 8: 151-157.
5. Castro ME, Pascual J, Romón T, Berciano J, Figols J, Pazos A (1998). 5-HT1B receptor binding in degenerative movement disorders. Brain Res 790: 323-328.
6. Chen CP, Alder JT, Bray L, Kingsbury AE, Francis PT, Foster OJ (1998). Post-synaptic 5-HT1A and 5-HT2A receptors are increased in Parkinson's disease neocortex. Ann N Y Acad Sci 861: 288-289.
7. Chou KL, Borek LL, Friedman JH (2007). The management of psychosis in movement disorder patients. Expert Opin Pharma-cother 8: 935-943.
8. Crespo-Facorro B, Kim JJ, Chemerinski E, Magnotta V, Andreasen NC, Nopoulos P (2004). Morphometry of the superior temporal plane in schizophrenia: relationship to clinical correlates. J Neuropsychiatry Clin Neurosci 16: 284-294.
9. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J (1994). The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 44: 2308-2314.
10. D'Amato RJ, Zweig RM, Whitehouse PJ, Wenk GL, Singer HS, Mayeux R, Price DL, Snyder SH (1987). Aminergic systems in Alzheimer's disease and Parkinson's disease. Ann Neurol 22: 229-236.
11. Diederich NJ, Fénelon G, Stebbins G, Goetz CG (2009). Hallucinations in Parkinson disease. Nat Rev Neurol 5: 331-342.
12. Factor SA, Feustel PJ, Friedman JH, Comella CL, Goetz CG, Kurlan R et al (2003). Longitudinal outcome of Parkinson's disease patients with psychosis. Neurology 60: 1756-1761. (Pubitemid 36737069)
13. Fenelon G, Mahieux F, Huon R, Ziegler M (2000). Hallucinations in Parkinson's disease: prevalence, phenomenology and risk factors. Brain 123(Part 4): 733-745.
14. Fernandez HH, Friedman JH, Jacques C, Rosenfeld M (1999). Quetiapine for the treatment of drug-induced psychosis in Parkinson's disease. Mov Disord 14: 484-487.
15. Fernandez HH, Aarsland D, Fenelon G, Friedman JH, Marsh L, Tröster AI et al (2008). Scales to assess psychosis in Parkinson's disease: critique and recommendations. Mov Disord 23: 484-500.
16. Fernandez HH, Trieschmann ME, Friedman JH (2003). Treatment of psychosis in Parkinson's disease: safety considerations. Drug Safety 26: 643-659.
17. Friedberg G, Zoldan J, Weizman A, Melamed E (1998). Parkinson Psychosis Rating Scale: a practical instrument for grading psychosis in Parkinson's disease. Clin Neuropharmacol 21: 280-284.
18. Friedman JH (1991). The management of the levodopa psychoses. Clin Neuropharmacol 14: 283-295.
19. Frieling H, Hillemacher T, Ziegenbein M, Neundörfer B, Bleich S (2007). Treating dopamimetic psychosis in Parkinson's disease: structured review and meta-analysis. Eur Neuropsychopharmacol 17: 165-171.
20. The French Clozapine Parkinson Study Group (1999). Clozapine in drug-induced psychosis in Parkinson's disease. Lancet 353: 2041-2042.
21. Goetz CG, Blasucci LM, Leurgans S, Pappert EJ (2000). Olanzapine and clozapine: comparative effects on motor function in hallucinating PD patients. Neurology 55: 789-794.
22. Goetz CG, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stebbins GT et al (2007). Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): process, format, and clinimetric testing plan. Mov Disord 22: 41-47.
23. Goetz CG, Leurgans S, Pappert EJ, Raman R, Stemer AB (2001). Prospective longitudinal assessment of hallucinations in Parkinson's disease. Neurology 57: 2078-2082.
24. Goetz CG, Poewe W, Rascol O, Sampaio C, Stebbins GT, Counsell C et al (2004). Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: status and recommendations. Mov Disord 19: 1020-1028.
25. Goetz CG, Vogel C, Tanner CM, Stebbins GT (1998). Early dopaminergic drug-induced hallucinations in parkinsonian patients. Neurology 51: 811-814.
26. Guy W (1976). Clinical global impressions. ECDEU Assessment Manual for Psychopharmacology, revised (DHEW Publ. No. ADM 76-338). National Institute of Mental Health: Rockville, MD. pp 218-222.
27. Holmes C, Arranz MJ, Powell JF, Collier DA, Lovestone S (1998). 5-HT2A and 5-HT2C receptor polymorphisms and psychopathology in late onset Alzheimer's disease. Hum Mol Genet 7: 1507-1509.
28. Johns MW (1991). A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 4: 540-545.
29. Kessler RM, Ansari MS, Riccardi P, Li R, Jayathilake K, Dawant B, Meltzer HY (2006). Occupancy of striatal and extrastriatal dopamine D2 receptors by clozapine and quetiapine. Neuropsy-chopharmacology 31: 1991-2001.
30. Kuroki T, Meltzer HY, Ichikawa J (1999). Effects of antipsychotic drugs on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens. Pharmacol Exp Ther 288: 774-781.
31. Lam LC, Tang NL, Ma SL, Zhang W, Chiu HF (2004). 5-HT2A T102C receptor polymorphism and neuropsychiatric symptoms in Alzheimer's disease. Int J Geriatr Psychiatry 19: 523-526.
32. Lewis JA (1999). Statistical principles for clinical trials (ICH 39): an introductory note on an international guideline. Stat Med 18: 1903-1942.
33. Mancini F, Tassorelli C, Martignoni E, Moglia A, Nappi G (2004). Long-term evaluation of the effect of quetiapine on hallucinations, delusions and motor function in advanced Parkinson disease. Clin Neuropharmacol 27: 33-37.
34. Meltzer HY, Arvanitis L, Bauer D, Rein W, Meta-Trial Study Group (2004). Placebo-controlled evaluation of four novel compounds for the treatment of schizophrenia and schizoaffective disorder. Am J Psychiatry 161: 975-984.
35. Meltzer HY, Kennedy J, Dai J, Parsa M, Riley D (1995). Plasma clozapine levels and the treatment of L-DOPA-induced psychosis in Parkinson's disease. A high potency effect of clozapine. Neuropsychopharmacol 12: 39-45.
36. Meltzer HY, Li Z, Kaneda Y, Ichikawa J (2003). Serotonin receptors: their key role in drugs to treat schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 27: 1159-1172.
37. i values. J Pharmacol Exp Ther 251: 238-246.
38. Meltzer HY, Stahl SM (1976). The dopamine hypothesis of schizophrenia: a review. Schizophr Bull 2: 19-76.
39. Merims D, Balas M, Peretz C, Shabtai H, Giladi N (2006). Rater-blinded, prospective comparison: quetiapine vs cloza-pine for Parkinson's disease psychosis. Clin Neuropharmacol 29: 331-337.
40. Miyasaki JM, Shannon K, Voon V, Ravina B, Kleiner-Fisman G, Anderson K et al (2006). Practice Parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 66: 996-1002. (Pubitemid 44044781)
41. Molho ES, Factor SA (1999). Worsening of motor features of parkinsonism with olanzapine. Mov Disord 14: 1014-1016.
42. Morgante L, Epifanio A, Spina E, Zappia M, Di Rosa AE, Marconi R et al (2004). Quetiapine and clozapine in parkinsonian patients with dopaminergic psychosis. Clin Neuropharmacol 27: 153-156. (Pubitemid 39121725)
43. Nichols DE (2004). Hallucinogens. Pharmacol Ther 101: 131-181.
44. Nocjar C, Roth BL, Pehek EA (2002). Localization of 5-HT(2A) receptors on dopamine cells in subnuclei of the midbrain A10 cell group. Neuroscience 111: 163-176.
45. Nordström AL, Farde L, Halldin C (1993). High 5-HT2 receptor occupancy in clozapine treated patients demonstrated by PET. Psychopharmacology (Berl) 110: 365-367.
46. Nordström AL, Farde L, Nyberg S, Karlsson P, Halldin C, Sedvall G (1995). D1, D2, and 5-HT2 receptor occupancy in relation to clozapine serum concentration: a PET study of schizophrenic patients. Am J Psychiatry 152: 1444-1449.
47. Ondo WG, Tintner R, Voung KD, Lai D, Ringholz G (2005). Double-blind, placebo-controlled, unforced titration parallel trial of quetiapine for dopaminergic-induced hallucinations in Parkinson's disease. Mov Disord 20: 958-963.
48. O'Neill MF, Heron-Maxwell CL, Shaw G (1999). 5-HT2 receptor antagonism reduces hyperactivity induced by amphetamine, cocaine, and MK-801 but not D1 agonist C-APB. Pharmacol Biochem Behav 63: 237-243.
49. Papapetropoulos S, Mash DC (2005). Psychotic symptoms in Parkinson's disease. From description to etiology. J Neurol 252: 753-764.
50. Parkinson Study Group (1999). Low-dose clozapine for the treatment of drug-induced psychosis in Parkinson's disease. N Engl J Med 340: 757-763.
51. Pehek EA, McFarlane HG, Maguschak K, Price B, Pluto CP (2001). M100,907, a selective 5-HT(2A) antagonist, attenuates dopamine release in the rat medial prefrontal cortex. Brain Res 888: 51-59.
52. Pessia M, Jiang ZG, North RA, Johnson SW (1994). Actions of 5-hydroxytryptamine on ventral tegmental area neurons of the rat in vitro. Brain Res 654: 324-330.
53. Pressler M, Nopoulos P, Ho BC, Andreasen NC (2005). Insular cortex abnormalities in schizophrenia: relationship to symptoms and typical neuroleptic exposure. Biol Psychiatry 57: 394-398. (Pubitemid 40215769)
54. Prisco S, Pagannone S, Esposito E (1994). Serotonin-dopamine interaction in the rat ventral tegmental area: an electrophysio-logical study in vivo. J Pharmacol Exp Ther 271: 83-90.
55. Pritchard AL, Harris J, Pritchard CW, Coates J, Haque S, Holder R et al (2008). Role of 5HT 2A and 5HT 2C polymorphisms in behavioural and psychological symptoms of Alzheimer's disease. Neurobiol Aging 29: 341-347.
56. Rabey JM, Prokhorov T, Miniovitz A, Dobronevsky E, Klein C (2006). Effect of quetiapine in psychotic Parkinson's disease patients: a double-blind labeled study of 3 months duration. Mov Disord 22: 313-318.
57. Ravina B, Marder K, Fernandez HH, Friedman JH, McDonald W, Murphy D et al (2007). Diagnostic criteria for psychosis in Parkinson's disease: report of an NINDS, NIMH work group. Mov Disord 22: 1061-1068.
58. Reddy S, Factor SA, Molho ES, Feustel PJ (2002). The effect of quetiapine on psychosis and motor function in parkinsonian patients with and without dementia. Mov Disord 17: 676-681.
59. Reynolds GP, Mason SL, Meldrum A, De Keczer S, Parnes H, Eglen RM, Wong EH (1995). 5-Hydroxytryptamine (5-HT)4 receptors in post mortem human brain tissue: distribution, pharmacology and effects of neurodegenerative diseases (1995). Br J Pharmacol 114: 993-998.
60. Romrell J, Fernandez HH, Okun MS (2003). Rationale for current therapies in Parkinson's disease. Exp Opin Pharmacother 4: 1747-1761.
61. Schmidt CJ, Fadayel GM, Sullivan CK, Taylor VL (1992). 5-HT2 receptors exert a state-dependent regulation of dopaminergic function: studies with MDL 100,907 and the amphetamine analogue, 3,4-methylenedioxymethamphetamine. Eur J Pharmacol 223: 65-74.
62. Shotbolt P, Samuel M, Fox C, David AS (2009). A randomized controlled trial of quetiapine for psychosis in Parkinson's disease. Neuropsychiatr Dis Treat 5: 327-332.
63. Vanover KE, Betz AJ, Weber SM, Bibbiani F, Kielaite A, Weiner DM et al (2008). A 5-HT2A receptor inverse agonist, ACP-103, reduces tremor in a rat model and levodopa-induced dyskinesias in a monkey model. Pharmacol Biochem Behav 90: 540-544.
64. Vanover KE, Weiner DM, Makhay M, Veinbergs I, Gardell LR, Lameh J et al (2006). Pharmacological and behavioral profile of N-(4-fluorophenylmethyl)-N-(1- methylpiperidin-4-yl)-N'-(4-(2-methylpropylo xy)phenylmethyl) carbamide (2R,3R)-dihydroxy-butanedioate (2:1) (ACP-103), a novel 5-hydroxytryptamine(2A) receptor inverse agonist. J Pharmacol Exp Ther 317: 910-918.
65. Waeber C, Palacios JM (1989). Serotonin-1 receptor binding sites in the human basal ganglia are decreased in Huntington's chorea but not in Parkinson's disease: a quantitative in vitro autoradiography study. Neuroscience 32: 337-347.
66. Wang PS, Schneeweiss S, Avorn J, Fischer MA, Mogun H, Solomon DH et al (2005). Risk of death in elderly users of conventional vs atypical antipsychotic medications. N Engl J Med 353: 2335-2341.
67. Weintraub D, Stern MB (2005). Psychiatric complications in Parkinson disease. Am J Geriatr Psychiatry 13: 844-851.
68. Wiesel FA, Farde L, Nordström AL, Sedvall G (1990). Central D1-and D2-receptor occupancy during antipsychotic drug treatment. Prog Neuropsychopharmacol Biol Psychiatry 14: 759-767.
69. Wint DP, Okun MS, Fernandez HH (2004). Psychosis in Parkinson's disease. J Geriatr Psychiatry Neurol 17: 127-136.
70. Wolters E (2006). PD-related psychosis: pathophysiology with therapeutical strategies. J Neural Transm 71(Suppl): 31-37.
71. Yan QS (2000). Activation of 5-HT2A/2C receptors within the nucleus accumbens increases local dopaminergic transmission. Brain Res Bull 51: 75-81.