Drug Insight: New drugs in development for Parkinson's disease

Nature Clinical Practice Neurology

Volumn 2, Issue 11, 2006, Pages 600-610

  Colosimo, Carlo ^a   Fabbrini, Giovanni ^a   Berardelli, Alfredo ^a  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

5 AMINO 2 (2 FURYL) 7 (2 PHENYLETHYL)PYRAZOLO[4,3 E][1,2,4]TRIAZOLO[1,5 C]PYRIMIDINE; 7 (4 METHYL 1 PIPERAZINYL) 2(3H) BENZOXAZOLONE; ANTIPARKINSON AGENT; ARUNDIC ACID; CEP 1347; CREATININE; ETIRACETAM; FIPAMEZOLE; GANGLIOSIDE GM1; GPI 1485; ISTRADEFYLLINE; LETEPRINIM; LEVODOPA; LEVODOPA METHYL ESTER; MINOCYCLINE; PLACEBO; PLANT EXTRACT; RASAGILINE; ROTIGOTINE; SAFINAMIDE; SARIZOTAN; SELEGILINE; TACROLIMUS; TALAMPANEL; TALIPEXOLE; UBIDECARENONE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VELVET BEAN EXTRACT; YOHIMBINE; ZONISAMIDE;

APPLICATION SITE REACTION; CARDIOVASCULAR SYMPTOM; CLINICAL TRIAL; DIZZINESS; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLASSIFICATION; DRUG DOSE REGIMEN; DRUG EFFECT; DRUG FORMULATION; DRUG HALF LIFE; DRUG MECHANISM; DRUG POTENTIATION; DRUG RESEARCH; DRUG SAFETY; DRUG STABILITY; DRUG TARGETING; DRUG WITHDRAWAL; ENZYME INHIBITION; FATIGUE; HUMAN; INSOMNIA; LOW DRUG DOSE; MAXIMUM PERMISSIBLE DOSE; MENTAL DISEASE; MOTOR DYSFUNCTION; NAUSEA; NEUROPROTECTION; NONHUMAN; PARKINSON DISEASE; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; SOMNOLENCE; THERAPY DELAY; TREATMENT DURATION; VELVET BEAN; VOMITING;

ANIMALS; ANTIPARKINSON AGENTS; DRUGS, INVESTIGATIONAL; HUMANS; NEUROPROTECTIVE AGENTS; PARKINSON DISEASE;

EID: 33750353036     PISSN: 1745834X     EISSN: 17458358     Source Type: Journal    
DOI: 10.1038/ncpneuro0340     Document Type: Review

References (85)

1. Nutt JG and Holford NH (1996) The response to levodopa in Parkinson's disease: Imposing pharmacological law and order. Ann Neurol 39: 561-573
2. Colosimo C and De Michele M (1999) Motor fluctuations in Parkinson's disease: Pathophysiology and treatment. Eur J Neurol 6: 1-21
3. Colosimo C et al. (1996) The motor response to acute dopaminergic challenge with apomorphine and levodopa in Parkinson's disease: implications or the pathogenesis of the on-off phenomenon. J Neurol Neurosurg Psychiatry 61: 634-637
4. Brotchie JM (2000) The neural mechanisms underlying levodopa-induced dyskinesia in Parkinson's disease. Ann Neurol 47 (Suppl 1): S105-S114
5. Bezard E et al. (2001) Pathophysiology of levodopa-induced dyskinesia: potential for new therapies. Nat Rev Neurosci 2: 577-588
6. Bedard PJ et al. (1992) Levodopa-induced dyskinesia: Facts and fancy. What does the MPTP monkey model tell us? Can J Neurol Sci 19: 134-137
7. Pearce RKB et al. (1998) De novo administration of ropinirole and bromocriptine induces less dyskinesia than LD in the MPTP-treated marmoset. Mov Disord 13: 234-241
8. Rascol O et al. (2000) A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa. 056 Study Group. N Engl J Med 342: 1484-1491
9. Parkinson Study Group (2004) Pramipexole vs levodopa as initial treatment for Parkinson disease: A 4-year randomized controlled trial. Arch Neurol 61: 1044-1053
10. Colosimo C et al. (1994) Clinical usefulness of apomorphine in movement disorders. Clin Neuropharmacol 17: 243-259
11. Brown RG and Marsden CD (1990) Cognitive function in Parkinson's disease: From description to theory. Trends Neurosci 13: 21-29
12. Senard JM et al. (2001) Orthostatic hypotension in patients with Parkinson's disease: Pathophysiology and management. Drugs Aging 18: 495-505
13. Bloem BR et al. (2004) Falls and freezing of gait in Parkinson's disease: A review of two interconnected, episodic phenomena. Mov Disord 19: 871-884
14. Pinto S et al. (2004) Treatments for dysarthria in Parkinson's disease. Lancet Neurol 3: 547-556
15. Wint DP et al. (2004) Psychosis in Parkinson's disease. J Geriatr Psychiatry Neurol 17: 127-136
16. Brotini S and Gigli GL (2004) Epidemiology and clinical features of sleep disorders in extrapyramidal disease. Sleep Med 5: 169-179
17. Johnston TH and Brotchie JM (2004) Drugs in development for Parkinson's disease. Curr Opin Investig Drugs 5: 720-726
18. Johnston TH and Brotchie JM (2006) Drugs in development for Parkinson's disease: An update. Curr Opin Investig Drugs 7: 25-32
19. Dawson TM and Dawson VL (2003) Molecular pathways of neurodegeneration in Parkinson's disease. Science 302: 819-822
20. Hirsch EC et al. (1999) Dopaminergic neurons degenerate by apoptosis in Parkinson's disease. Mov Disord 14: 383-385
21. Ravina BM et al. (2003) Neuroprotective agents for clinical trials in Parkinson's disease: A systematic assessment. Neurology 60: 1234-1240
22. Pålhagen S et al. (2006) Selegiline slows the progression of the symptoms of Parkinson disease. Neurology 66: 1200-1206
23. Parkinson Study Group (2002) A controlled trial of rasagiline in early Parkinson's disease (the TEMPO study). Arch Neurol 59: 1939-1943
24. Parkinson Study Group (2004) A controlled, randomized, delayed start study of rasagiline in early Parkinson's disease. Arch Neurol 61: 561-566
25. Shults CW et al. (2002) Effects of coenzyme Q10 in early Parkinson disease: Evidence for slowing of the functional decline. Arch Neurol 59: 1541-1550
26. Matthews RT et al. (1999) Creatine and cyclocreatine attenuate MPTP neurotoxicity. Exp Neurol 157: 142-149
27. NINDS NET-PD Investigators (2006) A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease. Neurology 66: 664-671
28. Currie LJ et al. (2004) Postmenopausal estrogen use affects the risk of Parkinson disease. Arch Neurol 61: 886-888
29. Dluzen D and Horstink M (2003) Estrogens as neuroprotectant of nigrostriatal dopaminergic system: Laboratory and clinical studies. Endocrine 21: 67-75
30. Schneider JS (1998) GM1 ganglioside in the treatment of Parkinson's disease. Ann NY Acad Sci 845: 363-373
31. Nobile Orazio E et al. (1994) Gangliosides: Their role in clinical neurology. Drugs 47: 576-585
32. Gold BG and Nutt JG (2002) Neuroimmunophilin ligands in the treatment of Parkinson's disease. Curr Opin Pharmacol 2: 82-86
33. Poulter MO et al. (2004) Neuroimmunophilins: A novel drug therapy for the reversal of neurodegenerative disease? Neuroscience 128: 1-6
34. Eberling JL et al. (2002) The immunophilin ligand GPI-1046 does not have neuroregenerative effects in MPTP-treated monkeys. Exp Neurol 178: 236-242
35. Lund S et al. (2005) Inhibition of microglial inflammation by the MLK inhibitor CEP-1347. J Neurochem 92: 1439-1451
36. Parkinson Study Group (2004) The safety and tolerability of a mixed lineage kinase inhibitor (CEP-1347) in PD. Neurology 62: 330-332
37. Du Y et al. (2001) Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson's disease. Proc Natl Acad Sci USA 98: 1469-1474
38. Steiger MJ et al. (1991) The clinical efficacy of oral levodopa methyl ester solution in reversing afternoon "off" periods in Parkinson's disease. Clin Neuropharmacol 14: 241-244
39. Nyholm D et al. (2005) Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease. Neurology 64: 216-223
40. Pearce RK et al. (2002) The monoamine reuptake blocker brasofensine reverses akinesia without dyskinesia in MPTP-treated and levodopa-primed common marmosets. Mov Disord 17: 877-886
41. Bara-Jimenez W et al. (2004) Effect of monoamine reuptake inhibitor NS2330 in advanced Parkinson's disease. Mov Disord 19: 1183-1186
42. Treatments in the PD pipeline: Parkinson pipeline project [http://www.pdpipeline.org/yy_treatmentdev/ treatment_list_2.htm#discontinued] (accessed 8 September 2006)
43. Rascol O et al. (1999) ABT-431, a D1 receptor agonist prodrug, has efficacy in Parkinson's disease. Ann Neurol 46: 736-741
44. Rascol O et al. (2001) Induction by dopamine D1 receptor agonist ABT-431 of dyskinesia similar to levodopa in patients with Parkinson disease. Arch Neurol 58: 249-254
45. Bezard E et al. (2003) Attenuation of levodopa-induced dyskinesia by normalizing dopamine D3 receptor function. Nat Med 9: 762-767
46. Stephenson DT et al. (2005) The effects of a selective D2 receptor agonist on behavioral and pathologic outcome in MPTP-treated squirrel monkeys. J Pharmacol Exp Ther 314: 1257-1266
47. Fabbrini G et al. (1988) Motor fluctuations in Parkinson's disease: central pathophysiological mechanisms part I. Ann Neurol 24: 366-371
48. Olanow CW et al. (2006) Drug Insight: Continuous dopaminergic stimulation in the treatment of Parkinson's disease. Nat Clin Pract Neurol 2: 382-392
49. Metman LV et al. (2001) Continuous transdermal dopaminergic stimulation in advanced Parkinson's disease. Clin Neuropharmacol 24: 163-169
50. Parkinson Study Group (2003) A controlled trial of rotigotine monotherapy in early Parkinson's disease. Arch Neurol 60: 1721-1728
51. Woitalla D et al. (2004) Transdermal lisuride delivery in the treatment of Parkinson's disease. J Neural Transm Suppl 68: S89-S95
52. Wolf WA (2003) SLV-308: Solvay. Curr Opin Investig Drugs 4: 878-882
53. Fariello RG et al. (1998) Preclinical evaluation of PNU-151774E as a novel anticonvulsant. J Pharmacol Exp Ther 285: 397-403
54. Stocchi F et al. (2004) Improvement of motor function in early Parkinson disease by safinamide. Neurology 63: 746-748
55. 2A antagonist: A novel antiparkinsonian agent that does not provoke dyskinesia in parkinsonian monkeys. Ann Neurol 43: 507-513
56. Kostic VS et al. (1999) Theophylline increases "on" time in advanced parkinsonian patients. Neurology 52: 1916
57. 2A antagonist theophylline in Parkinson's disease. Clin Neuropharmacol 25: 25-31
58. Hauser RA et al. (2003) Istradefylline US-001 Study Group: Randomized trial of the adenosine A2A receptor antagonist istradefylline in advanced PD. Neurology 61: 297-303
59. Results of phase-III clinical studies of an anti-Parkinson's disease drug istradefylline (KW-6002) conducted overseas [http://www.leaddiscovery.co.uk/prlink.asp?reclink=http://www.kyowa.co.jp/ eng/netext/er060307.htm] (accessed 8 September 2006)
60. Papa SM et al. (1999) Internal globus pallidus discharge is nearly suppressed during levodopa induced dyskinesias. Ann Neurol 46: 732-738
61. Colosimo C and Craus A (2003) Noradrenergic drugs for levodopa-induced dyskinesia. Clin Neuropharmacol 26: 299-305
62. Gomez-Mancilla B and Bèdard PJ (1993) Effect of nondopaminergic drugs on L-dopa-induced dyskinesias in MPTP-treated monkeys. Clin Neuropharmacol 16: 418-427
63. Chase TN et al. (2000) Antiparkinsonian and antidyskinetic activity of drugs targeting central glutamatergic mechanisms. J Neurol 247 (Suppl 2): S36-S42
64. Metman LV et al. (1998) Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson's disease. Neurology 50: 1323-1326
65. Snow BJ et al. (2000) The effect of amantadine on levodopa-induced dyskinesias in Parkinson's disease: A double-blind, placebo-controlled study. Clin Neuropharmacol 23: 82-85
66. Thomas A et al. (2004) Duration of amantadine benefit on dyskinesia of severe Parkinson's disease. J Neurol Neurosurg Psychiatry 75: 141-143
67. Steece-Collier K et al. (2000) Antiparkinsonian actions of CP-101,606, an antagonist of NR2B subunit-containing N-methyl-D-aspartate receptors. Exp Neurol 163: 239-243
68. Scheinin M et al. (1994) Distribution of α2-adrenergic receptor subtype gene expression in rat brain. Brain Res Mol Brain Res 21: 133-149
69. Hill MP and Brotchie JM (1999) The adrenergic receptor agonist, clonidine, potentiates the anti-parkinsonian action of the selective kappa-opioid receptor agonist, enadoline, in the monoamine-depleted rat. Br J Pharmacol 128: 1577-1585
70. Reisine TD et al. (1982) A role for striatal beta-adrenergic receptors in the regulation of dopamine release. Brain Res 241: 123-130
71. Burn DJ (2002) Depression in Parkinson's disease. Eur J Neurol 9 (Suppl 3): S44-S54
72. Chopin P et al. (1986) The effects of yohimbine on exploratory and locomotor behavior are attributable to its effects at noradrenaline and not at benzodiazepine receptor. Neuropharmacology 25: 53-57
73. Savola JM et al. (2003) Fipamezole (JP-1730) is a potent alpha-2-adrenergic receptor antagonist that reduces levodopa-induced dyskinesia in the MPTP-lesioned primate model of Parkinson's disease. Mov Disord 18: 872-883
74. Carpentier AF et al. (1996) Improvement of levodopa-induced dyskinesia by propranolol in Parkinson's disease. Neurology 46: 1548-1551
75. Henry B et al. (1999) The alpha2-adrenergic receptor antagonist idazoxan reduces dyskinesia and enhances anti-parkinsonian actions of L-dopa in the MPTP-lesioned primate model of Parkinson's disease. Mov Disord 14: 744-753
76. Rascol O et al. (2001) Idazoxan, an alpha-2 antagonist, and L-DOPA-induced dyskinesias in patients with Parkinson's disease. Mov Disord 16: 708-713
77. Manson AJ et al. (2000) Idazoxan is ineffective for levodopa-induced dyskinesia in Parkinson's disease. Mov Disord 15: 336-337
78. Bezard E et al. (2003) Presymptomatic compensation in Parkinson's disease is not dopamine-mediated. Trends Neurosci 26: 215-221
79. Bibbiani F et al. (2001) Serotonin 5-HT1A agonist improves motor complications in rodent and primate parkinsonian models. Neurology 57: 1829-1834
80. Olanow CW et al. (2004) Open-label trial of sarizotan in Parkinson disease patients with levodopa-induced dyskinesias (the SPLENDID Study). Clin Neuropharmacol 27: 58-62
81. Bara-Jimenez W et al. (2005) Effects of serotonin 5-HT1A agonist in advanced Parkinson's disease. Mov Disord 20: 932-936
82. Kumar SP and Smith PE (2004) Levetiracetam as add-on therapy in generalised epilepsies. Seizure 13: 475-477
83. Bezard E et al. (2003) Novel antiepileptic drug levetiracetam decreases dyskinesia elicited by L-dopa and ropinirole in the MPTP-lesioned marmoset. Mov Disord 18: 1301-1305
84. Zesiewicz TA et al. (2005) Open-label pilot study of levetiracetam (Keppra) for the treatment of levodopa-induced dyskinesias in Parkinson's disease. Mov Disord 20: 1205-1209
85. Lyons KE and Pahwa R (2006) Efficacy and tolerability of levetiracetam in Parkinson disease patients with levodopa-induced dyskinesia. Clin Neuropharmacol 29: 148-153