Double-blind, controlled phase ii study of a 5-ht6 receptor antagonist, sb-742457, in alzheimer's disease

Current Alzheimer Research

Volumn 7, Issue 5, 2010, Pages 374-385

  Maher Edwards, Gareth ^a   Zvartau Hind, M ^a   Hunter, A J ^a   Gold, M ^b   Hopton, G ^a   Jacobs, G ^a   Davy, M ^a   Williams, P ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

^b GLAXOSMITHKLINE   (United States)

Author keywords

5 ht6; Alzheimer's disease; Cognition; Global function; SB 742457; Serotonin

Indexed keywords

3 PHENYLSULFONYL 8 (1 PIPERAZINYL)QUINOLINE; APOLIPOPROTEIN E4; PLACEBO;

ADULT; AGED; ALZHEIMER DISEASE; ARTICLE; CLINICAL TRIAL; COGNITION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; DISEASE SEVERITY; DIZZINESS; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG FATALITY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FALLING; FEMALE; HEADACHE; HUMAN; MAJOR CLINICAL STUDY; MALE; MINI MENTAL STATE EXAMINATION; MULTICENTER STUDY; NAUSEA; PATIENT COMPLIANCE; PERIPHERAL EDEMA; PHASE 2 CLINICAL TRIAL; POLLAKISURIA; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; SCORING SYSTEM; SIDE EFFECT; TREATMENT DURATION; UNSPECIFIED SIDE EFFECT; URINARY TRACT INFECTION; VOMITING;

AGED; AGED, 80 AND OVER; ALZHEIMER DISEASE; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FEMALE; HUMANS; MALE; MIDDLE AGED; QUINOLINES; RECEPTORS, SEROTONIN; SEROTONIN ANTAGONISTS; SINGLE-BLIND METHOD; SULFONES;

EID: 77957240989     PISSN: 15672050     EISSN: None     Source Type: Journal    
DOI: 10.2174/156720510791383831     Document Type: Article

References (44)

1. Altman HJ, Normile HJ. What is the nature of the role of the serotonergic nervous system in learning and memory: prospects for development of an effective treatment strategy for senile dementia. Neurobiol Aging 9: 627-638 (1988).
2. Schmitt JA, Wingen M, Ramaekers JG, Evers EA, Riedel W. Serotonin and human cognitive performance. Curr Pharm Des 12: 2473-2486 (2006).
3. Bowen DM, Procter AW, Mann DM, Snowden JS, Esiri MM, Neary D, et al. Imbalance of a serotonergic system in frontotemporal dementia: implication for pharmacotherapy. Psychopharmacology (Berl) 196: 603-610 (2008).
4. Mitchell ES, Neumaier JF. 5-HT6 receptors: a novel target for cognitive enhancement. Pharmacol Ther 108: 320-333 (2005).
5. Lane HY, Liu YC, Huang CL, Hsieh CL, Chang YL, Chang L, et al. Prefrontal executive function and D1, D3, 5-HT2A and 5-HT6 receptor gene variations in healthy adults. J Psychiatry Neurosci 33: 47-53 (2008).
6. Lane HY, Lin CC, Huang CH, Chang YC, Hsu SK, Chang WH. Risperidone response and 5-HT6 receptor gene variance: genetic association analysis with adjustment for nongenetic confounders. Schizophr Res 67: 63-70 (2004).
7. Garcia-Alloza M, Hirst WD, Chen CP, Lasheras B, Francis PT, Ramírez MJ. Differential involvement of 5-HT(1B/1D) and 5-HT6 receptors in cognitive and non-cognitive symptoms in Alzheimer's disease. Neuropsychopharmacology 29: 410-416 (2004).
8. Marcos B, García-Alloza M, Gil-Bea FJ, Chuang TT, Francis PT, Chen CP, et al. Involvement of an altered 5-HT receptor function in behavioral symptoms of Alzheimer's disease. J Alzheimers Dis 14: 43-50 (2008).
9. Bentley JC, Sleight AJ, Marsden CA, Fone KFC. 5-HT6 antisense oligonucleotide i.c.v. affects rat performance in the water maze and feeding. J Psychopharmacol 11(3 suppl): A64 (1997).
10. Rogers DC, Hagan JJ. 5-HT6 receptor antagonists enhance retention of a water maze task in the rat. Psychopharmacology (Berl) 158: 114-119 (2001).
11. Woolley ML, Bentley JC, Sleight AJ, Marsden CA, Fone KC. A role for 5-ht6 receptors in retention of spatial learning in the Morris water maze. Neuropharmacology 41: 210-219 (2001).
12. King MV, Sleight AJ, Woolley ML, Topham IA, Marsden CA, Fone KC. 5-HT6 receptor antagonists reverse delay-dependent deficits in novel object discrimination by enhancing consolidation-an effect sensitive to NMDA receptor antagonism. Neuropharmacology 47: 195-204 (2004).
13. Woolley ML, Marsden CA, Sleight AJ, Fone KC. Reversal of a cholinergic-induced deficit in a rodent model of recognition memory by the selective 5-HT6 receptor antagonist, Ro 04-6790. Psychopharmacology (Berl) 170: 358-367 (2003).
14. Hirst WD, Stean TO, Rogers DC, Sunter D, Pugh P, Moss SF, et al. SB-399885 is a potent, selective 5-HT6 receptor antagonist with cognitive enhancing properties in aged rat water maze and novel object recognition models. Eur J Pharmacol 553: 109-119 (2006).
15. Meneses A. Role of 5-HT6 receptors in memory formation. Drug News Perspect 14: 396-400 (2001).
16. Riemer C, Borroni E, Levet-Trafit B, Martin JR, Poli S, Porter RH, et al. Influence of the 5-HT6 receptor on acetylcholine release in the cortex: pharmacological characterization of 4-(2-bromo-6-pyrrolidin-1-ylpyridine-4-sulfonyl)phenylamine, a potent and selective 5-HT6 receptor antagonist. J Med Chem 46: 1273-1276 (2003).
17. Foley AG, Murphy KJ, Hirst WD, Gallagher HC, Hagan JJ, Upton N, et al. The 5-HT(6) receptor antagonist SB-271046 reverses scopolamine-disrupted consolidation of a passive avoidance task and ameliorates spatial task deficits in aged rats. Neuro-psychopharma-cology 29: 93-100 (2004).
18. Chuang ATT, Foley A, Pugh PL. 5-HT6 receptor antagonist SB-742457 as a novel cognitive enhancing agent for Alzheimer's disease. Alzheimers Dement 2: S631-632 (2006).
19. Upton N, Chuang TT, Hunter AJ, Virley DJ. 5-HT6 receptor antagonists as novel cognitive enhancing agents for Alzheimer's disease. Neurotherapeutics 5: 458-469 (2008).
20. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer's disease. Neurology 34: 939-944 (1984).
21. Folstein MF, Folstein SE, McHugh PR. Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12: 189-198 (1975).
22. Ráman GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 43: 250-260 (1993).
23. Risner ME, Saunders AM, Altman JF, Ormandy GC, Craft S, Foley IM, et al. Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease. Pharmacogenomics J 6: 246-254 (2006).
24. Schneider LS, Olin JT, Doody RS, Clark CM, Morris JC, Reisberg B, et al. Validity and reliability of the Alzheimer's disease cooperative study-clinical global impression of change. The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord 11 (Suppl 2): S22-32 (1997).
25. Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer's disease. Am J Psychiatry 141: 1356-1364 (1984).
26. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 44:2308-2314 (1994).
27. Gélinas I, Gauthier L, McIntyre M, Gauthier S. Development of a functional measure for persons with Alzheimer's disease: the disability assessment for dementia. Am J Occup Ther 53: 471-481 (1999).
28. Doward LC. The development of the Alzheimer's Carers' Quality of Life Instrument (ACQLI) [Abstr 88]. Qual Life Res 6(suppl 7-8): 639 (1997).
29. Gordon B, Carson K. The basis for choice reaction time slowing in Alzheimer's disease. Brain Cogn 13: 148-166 (1990).
30. Fray PJ, Robbins TW, Sahakian BJ. Neuropsychiatric applications of CANTAB. Int J Geriatr Psychiatry 11: 329-336 (1996).
31. Burns A, Rossor M, Hecker J, Gauthier S, Petit H, Möller HJ, et al. The effects of donepezil in Alzheimer's disease-Results from a multinational trial. Dement Geriatr Cogn Disord 10: 237-244 (1999).
32. ® [package insert]. Woodcliff Lake, NJ: Eisai Co, Ltd; 2006. Available at: http://www.aricept.com. Accessed October 15,2008].
33. Stern RG, Mohs RC, Davidson M, Schmeidler J, Silverman J, Kramer-Ginsberg E, et al. A longitudinal study of Alzheimer's disease: measurement, rate, and predictors of cognitive deterioration. Am J Psychiatry 151: 390-396 (1994).
34. Raskind MA, Peskind ER, Wessel T, Yuan W. Galantamine in AD: a 6-month randomized, placebo-controlled trial with a 6-month extension. The Galantamine USA-1 Study Group. Neurology 54: 2261-2268 (2000).
35. Maher-Edwards G, Dixon R, Hunter J, Gold M, Hopton G, Hunter J, et al. Efficacy and tolerability of SB-742457, a 5HT6 receptor antagonist, and donepezil in subjects with mild-to-moderate Alzheimer's disease. 11th International Conference on Alzheimer's Disease. Alzheimers Dement 4(suppl 2): T772-T773 (2008).
36. Bakchine S, Loft H. Memantine treatment in patients with mild to moderate Alzheimer's disease: results of a randomised, double blind, placebo-controlled 6-month study. J Alzheimers Dis 13:97-107 (2008).
37. Gold M. Study design factors and patient demographics and their effect on the decline of placebo-treated patients in randomised clinical trials in Alzheimer's disease. J Clin Psychiatry 68: 430-438 (2007).
38. Aisen PS, Schneider LS, Sano M, Diaz-Arrastia R, van Dyck CH, Weiner MF, et al. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA 300: 1774-1783 (2008).
39. Kurz A, Farlow M, Quarg P, Spiegel R. Disease stage in Alzheimer disease and treatment effects of rivastigmine. Alzheimer Dis Assoc Disord 18: 123-128 (2004).
40. de Jong D, Jansen R, Hoefnagels W, Jellesma-Eggenkamp M, Verbeek M, Borm G, et al. No effect of one-year treatment with indomethacin on Alzheimer's disease progression: a randomized controlled trial. PLoS ONE 3(1): e1475 (2008).
41. Sevigny JJ, Ryan JM, van Dyck CH, Peng Y, Lines CR, Nessly ML. Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial. Neurology 71(21): 1702-1708 (2008).
42. Irizarry MC, Webb DJ, Bains C, Barrett SJ, Lai RY, Laroche JP, et al. Predictors of placebo group decline in the Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) in 24 week clinical trials of Alzheimer's disease. J Alzheimers Dis 14: 301-311 (2008).
43. Birks J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev 1: CD005593 (2006).
44. Koch G, Zinc RC. SAS MacroNparCov version 2 - Non-Parametric Analysis of Covariance-Users Guide (2002).