Syl<strong>la</strong>bus 09 2-10-2009 10:31 Pagina 160Alcuni farmaci precursori <strong>di</strong> sostanze fisiologicamente presenti nell’organismo cheagiscono come antiossidanti, come ad esempio l’urato, sembrano inoltre associati aun ritardo nell’inizio <strong>di</strong> terapia dopaminergica nei pazienti con ma<strong>la</strong>ttia <strong>di</strong>Parkinson. Uno stu<strong>di</strong>o recente ha infatti mostrato che pazienti in fasi iniziali <strong>di</strong>ma<strong>la</strong>ttia con elevati livelli <strong>di</strong> urato iniziano <strong>la</strong> terapia sintomatica due anni doporispetto a quelli con più bassi livelli p<strong>la</strong>smatici <strong>di</strong> urato, mostrando inoltre, all’indaginestrumentale, una minor progressione annuale <strong>di</strong> ma<strong>la</strong>ttia (10). L’inosina, precursoredell’urato, somministrata <strong>per</strong> via orale determina un incremento dei valoriematici <strong>di</strong> urato fino al doppio dei valori fisiologici, potendo quin<strong>di</strong> svolgere funzionineuroprotettive. Stu<strong>di</strong> in corso stanno valutando <strong>la</strong> capacità dell’inosina, assunta<strong>per</strong> via orale, <strong>di</strong> incrementare i valori non solo p<strong>la</strong>smatici ma anche liquorali <strong>di</strong>urato.160
Syl<strong>la</strong>bus 09 2-10-2009 10:31 Pagina 161BIBLIOGRAFIA1. Poewe W. Treatments for Parkinson <strong>di</strong>sease-past achievements and current clinicalneeds. Neurology. 2009; 72(7 Suppl):S65-73.2. Fox SH, Brotchie JM, Lang AE. Non-dopaminergic treatments in developmentfor Parkinson’s <strong>di</strong>sease. Lancet Neurol. 2008; 7(10):927-38.3. Hauser RA, Bronzova J, Sampaio C, et al.Safety and tolerability of pardoprunox,a new partial dopamine agonist, in a randomized, controlled study ofpatients with advanced Parkinson’s <strong>di</strong>sease. Eur Neurol. 2009;62(1):40-8.4. Stocchi F, Arnold G, Onofrj M, et al. Improvement of motor function in earlyParkinson <strong>di</strong>sease by Safinamide. Neurology. 2004; 63(4):746-8.5. LeWitt PA, Guttman M, Tetrud JW . Adenosine A2A receptor antagonist istradefylline(KW-6002) reduces “off” time in Parkinson’s <strong>di</strong>sease: a double-blind, randomized,multicenter clinical trial (6002-US-005). Ann Neurol. 2008; 63(3):295-302.6. Murata M, Hasegawa K, Kanazawa I et al. Zonisamide improves motor function inParkinson <strong>di</strong>sease: a randomized, double-blind study. Neurology. 2007; 68(1):45-50.7. Ry<strong>la</strong>nder D, Recchia A, Me<strong>la</strong> F, et al. Pharmacological modu<strong>la</strong>tion of glutamatetransmission in a rat model of L-DOPA-induced dyskinesia: effects on motor behaviorand striatal nuclear signaling. J Pharmacol Exp Ther. 2009;330(1):227-358. Goetz CG, Damier p, Hicking C et al. SArizotan as a treatment for dyskinesiasin Parkinson’s <strong>di</strong>sease: a DB-PBO trial. Mov Disord 2007; 22: 179-186.9. Chan CS, Guzman JN, Ilijic E, et al. ‘Rejuvenation’ protects neurons in mousemodels of Parkinson’s <strong>di</strong>sease. Nature. 2007 447(7148):1081-6.10 Weisskopf MG, O’Reilly E, Chen H et al. P<strong>la</strong>sma urate and risk of Parkinson’s<strong>di</strong>sease. Am J Epidemiol. 2007 166:561-7.11. http://www.clinicaltrials.govTabel<strong>la</strong> 1: Farmaci attualmente in stu<strong>di</strong>o in trials randomizzati control<strong>la</strong>ti (11)Farmaco Meccanismo d’azione Fase stu<strong>di</strong>oIPX066 Levodopa ER 3Pardoprunox (SLV308) Agonista parziale D2/D3 3Safinamide Inibitore MAO-B /inibitore del ri<strong>la</strong>scio GLU 3Pimavanserina ACP103) Antagonista 5 HT2A 2AFQ056 Antagonista mGluR5 2Fipamezolo Antagonista adrenergico alfa2 2bIstradefillina Antagonista recettori adenosinici A 2a 2-3Piclozotan Agonista 5 HT1A 2Pramipexolo Agonista Dopaminergico 4Inosina Precursore dell’urato 2161