Continuous Dopaminergic Stimulation in Parkinson’s Disease
provide stable and more prolonged synaptic levels of striatal DA compared with standard levodopa administration along with a sustained motor response.
Discussion
To our knowledge, there are no PET studies that have directly tested whether currently available drug approaches, which provide more sustained levodopa delivery, also provide stable and more prolonged synaptic levels of striatal DA along with a sustained motor response. However, it is clear that PET has a great potential in this specific research field and could provide valuable insight on the pharmacokinetics and pharmacodynamics of new agents and therapeutic strategies in PD. First, the entacapone and tolcapone experience clearly indicates that quantitative 18F-dopa PET may be useful in assessing pharmacological manipulations of levadopa delivery into the brain. Late imaging can be informative if central COMT inhibition needs to be demonstrated. More importantly, sequential 11C-raclopride PET scans can be used to compare the effects of intermittent and continuous dopaminergic delivery directly on striatal DA levels in PD patients. The same paradigm may also be useful to examine whether pulsatile and continuous dopaminergic stimulation have different long-term effects on pre-synaptic function and on the ability of the striatum to release DA in the synaptic cleft following an acute levodopa challenge. n
1.
Nutt JG, Obeso JA, Stocchi F, Continuous dopamine- receptor stimulation in advanced Parkinson's disease, Trends Neurosci, 2000;23(Suppl. 10):S109–15.
2. Stocchi F, Olanow CW, Continuous dopaminergic stimulation in early and advanced Parkinson's disease, Neurology, 2004;62(1 Suppl. 1):S56-63.
3.
Olanow CW, Obeso JA, Stocchi F, Continuous dopamine- receptor treatment of Parkinson's disease: scientific rationale and clinical implications, Lancet Neurol, 2006; 5:677–87.
4.
Sawle GV, Burn DJ, Morrish PK, et al., The effect of entacapone (OR-611) on brain [18F]-6-L-fluorodopa metabolism: implications for levodopa therapy of Parkinson’s disease, Neurology, 1994;44:1292–7.
5.
Ishikawa T, Dhawan V, Chaly T, et al., Fluorodopa positron emission tomography with an inhibitor of catechol-O-methyltransferase: effect of the plasma 3-O- methyldopa fraction on data analysis, J Cereb Blood Flow Metab, 1996;16:854–63.
6.
Ruottinen HM, Rinne JO, Ruotsalainen UH, et al., Striatal [18F]fluorodopa utilization after COMT inhibition with entacapone studied with PET in advanced Parkinson's disease, J Neural Transm Park Dis Dement Sect, 1995;10:91–106.
7.
Ruottinen HM, Rinne JO, Oikonen VJ, et al., Striatal 6-[18F]fluorodopa accumulation after combined inhibition of peripheral catechol-O-methyltransferase and monoamine oxidase type B: differing response in relation to presynaptic dopaminergic dysfunction, Synapse, 1997;27:336–46.
8. 9.
Ceravolo R, Piccini P, Bailey DL, et al., 18F-dopa PET evidence that tolcapone acts as a central COMT inhibitor in Parkinson's disease, Synapse, 2002;43(3):201–7.
Zurcher G, Dingemanse J, Da Prada M, Potent COMT inhibition by Ro 40-7592 in the periphery ad in the brain, Adv Neurol, 1993;60:641–647.
18. 10.
David J Brooks is the Hartnett Professor of Neurology and Head of the Centre for Neuroscience in the Department of Medicine at Imperial College London. He is also a Senior Neurologist in Medical Diagnostics at GE Healthcare PLC. His research involves the use of positron-emission tomography and magnetic resonance imaging to diagnose and study the progression of Alzheimer’s and Parkinson’s disease and their validation of biomarker therapeutic trials. To
date, he has published over 300 reports in peer-reviewed journals, including Nature. Professor Brooks’ research is supported by grants from the UK Medical Research Council, the Alzheimer’s Research Trust, the UK Parkinson’s Disease Society, the Michael J Fox Foundation and industry. He has been an active member of the research advisory panels and boards for many of the leading Parkinson’s disease and neurology societies and is on the Editorial Boards of Brain, the Journal of Neural Transmission, Synapse, Molecular Imaging and Biology, Neurotherapeutics and Current Trends in Neurology. He is a Fellow of the UK’s Academy of Medical Science and has been the invited keynote speaker at several prestigious international scientific meetings.
Nicola Pavese is a Senior Investigator Scientist based at the Medical Research Council – Neurology PET Group in London and an Honorary Senior Lecturer at Imperial College London. His research activity has focused on the neuropharmacology and neurochemistry of movement disorders and he is investigating pathogenetic mechanisms underlying non-motor symptoms of Parkinson’s disease by using functional imaging techniques.
Duodet DJ, Chan GL, Holden JE, et al., Effects of monoamineoxydase and catechol-O-methyltransferase inhibition on dopamine turnover: a PET study with 6-[18F]L-DOPA, Eur J Pharmacol, 1997;334:31–8.
11. 12.
Laruelle M, Imaging synaptic neurotransmission with in vivo binding competition techniques: a critical review, J Cereb Blood Flow Metab, 2000;20:423–51.
Rinne JO, Laihinen A, Rinne UK, et al., PET study on striatal dopamine D2 receptor changes during the progression of early Parkinson's disease, Mov Disord, 1993;8:134–8.
13.
Sawle GV, Playford ED, Brooks DJ, et al., Asymmetrical pre-synaptic and post-synpatic changes in the striatal dopamine projection in dopa naive parkinsonism. Diagnostic implications of the D2 receptor status, Brain, 1993;116:853–67.
14.
Turjanski N, Lees AJ, Brooks DJ, In vivo studies on striatal dopamine D1 and D2 site binding in dopa-treated Parkinson’s disease patients with and without dyskinesias, Neurology, 1997;49:717–23.
15.
Shinotoh H, Hirayama K, Tateno Y, Dopamine D1 and D2 receptors in Parkinson's disease and striatonigral degeneration determined by PET, Adv Neurol, 1993;60: 488–93.
16.
Antonini A, Vontobel P, Psylla M, et al., Complementary positron emission tomographic studies of the striatal dopaminergic system in Parkinson’s disease, Arch Neurol, 1995;52:1183–90.
17.
Antonini A, Schwarz J, Oertel WH, et al., Long-term changes of striatal dopamine D2 receptors in patients with Parkinson's disease: a study with positron emission tomography and [11C]raclopride, Mov Disord, 1997;12:33–8.
Dentresangle C, Veyre L, Le Bars D, et al., Striatal D2 dopamine receptor status in Parkinson's disease: an [18F]Dopa and [11C]-raclopride PET study, Mov Disord,
24. 20.
1999,14:1025–30. 19.
Uitti RJ, Vingerhoets FJ, Hayward M, et al., Positron emission tomography (PET) measurements of striatal D(2) receptors in untreated Parkinson's disease patients with follow-up after 6 and 12 months' treatment with SINEMET® or SINEMET® CR, Parkinsonism Relat Disord, 1997;3:43–6.
Shinotoh H, Inoue O, Hirayama K, et al., Dopamine D1 receptors in Parkinson's disease and striatonigral degeneration: a positron emission tomography study, J Neurol Neurosurg Psychiatry, 1993;56:467–72.
21.
Breier A, Sur TP, Saunders R, et al., Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations, Proc Natl Acad Sci, 1997;94: 2569–74.
22.
Tedroff J, Pedersen M, Aquilonius SM, et al., Levodopa- induced changes in synaptic dopamine in patients with Parkinson's disease as measured by [11C]raclopride displacement and PET, Neurology, 1996;46:1430–36.
23.
de la Fuente-Fernandez R, Lu JQ, Sossi V, et al., Biochemical variations in the synaptic level of dopamine precede motor fluctuations in Parkinson's disease: PET evidence of increased dopamine turnover, Ann Neurol, 2001;49:298–303.
de la Fuente-Fernandez R, Sossi V, Huang Z, et al., Levodopa-induced changes in synaptic dopamine levels increase with progression of Parkinson's disease: implications for dyskinesias, Brain, 2004;127:2747–54.
25. 26.
Pavese N, Evans AH, Tai YF, et al., Clinical correlates of levodopa-induced dopamine release in Parkinson disease: a PET study, Neurology, 2006:14;67(9):1612–17.
Sossi V, de la Fuente-Fernández R, Schulzer M, et al., Dopamine transporter relation to dopamine turnover in Parkinson's disease: a positron emission tomography study, Ann Neurol, 2007;62:468–74.
EUROPEAN NEUROLOGICAL REVIEW
25
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100 |
Page 101 |
Page 102 |
Page 103 |
Page 104 |
Page 105 |
Page 106 |
Page 107 |
Page 108 |
Page 109 |
Page 110 |
Page 111 |
Page 112 |
Page 113 |
Page 114 |
Page 115 |
Page 116