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Review

Novel pharmacological strategies for motor complications in Parkinson’s disease

Pages 377-392 | Published online: 22 Apr 2005

Bibliography

  • DE RIJK MC, LAUNER L, BERGER K et al: Prevalence of Parkinson's disease in Europe: a collaborative study of population-based cohorts. Neurology (2000) 54(11 Suppl. 5):S21–S23.
  • SCHRAG A, QUINN N: Dyskinesias and motor fluctuations in Parkinson's disease. A community-based study. Broth (2000) 123(11):2297–2305.
  • FAHN S: The spectrum of levodopa-induced dyskinesias. Ann. Neurol (2000) 47\(Suppl. 1):2–11.
  • METMAN LV, KONITSIOTIS S, CHASE TN: Pathophysiology of motor response complications in Parkinson's disease: hypotheses on the why, where, and what. Mov. Disord. (2000) 15(1):3–8.
  • CHASE TN, KONITSIOTIS S, OH JD: Striatal molecular mechanisms and motor dysfunction in Parkinson's disease. Adv. Neurol (2001) 86:355–360.
  • CHASE TN, OH JD: Striatal dopamine-and glutamate-mediated dysregulation in experimental Parkinsonism. Trends Neurosci. (2000) 23(10):586–591.
  • ••A review describing the striatal molecularchanges underlying the development of MRCs.
  • CHASE TN, OH JD: Striatal mechanisms and pathogenesis of Parkinsonian signs and motor complications. Ann. Neurol (2000) 47(4):5122–5130.
  • PICCONI B, CENTONZE D, HAKANSSON K et al: Loss of bidirectional striatal synaptic plasticity in L-dopa induced dyskinesias. Nature Neurosci. (2003) 6:501–506.
  • BROTCHIE JM: The neural mechanisms underlying levodopa-induced dyskinesia. Ann. Neurol (2000) 47\(Suppl. 1):105–114.
  • •Detailed review on the pathophysiology of LD-induced dyskinesia.
  • CHASE TN: The significance of continuous dopaminergic stimulation in the treatment of Parkinson's disease. Drugs (1998) 55(1):1–9.
  • •A review on the theoretical and experimental evidence supporting the concept of continuous dopaminergic stimulation.
  • OLANOW W, SCHAPIRA AH, RASCOL 0: Continuous dopamine-receptor stimulation in early Parkinson's disease. Trends Neurosci. (2000) 23(10):S117–S126.
  • PEARCE RK, BANERJI T, JENNER P, MARSDEN CD: De novo administration of ropinirole and bromocriptine induces less dyskinesia than L-dopa in the MPTP-treated marmoset. Mov. Disord. (1998)13:234–241.
  • HADJ TAHAR A, GREGOIRE L, BANGASSORO E, BEDARD PJ: Sustained cabergoline treatment reverses levodopa-induced dyskinesias in Parkinsonian monkeys. Clin. Neuropharmacol (2000) 23:195–202.
  • MARATOS EC, JACKSON MJ, PEARCE RK, JENNER P: AntiParkinsonian activity and dyskinesia risk of ropinirole and L-DOPA combination therapy in drug naive MPTP-lesioned common marmosets (Callithrixjacchus). Mov. Disord. (2001) 16:631–641.
  • STOCCHI F, VACCA L, BERARDELLI A, DE PANDIS F, RUGGIERI S: Long- duration effect and the postsynaptic compartment: study using a dopamine agonist with a short half-life. Mov. Disord. (2001) 16:301–305.
  • STOCCHI F, RUGGIERI S, VACCA L, OLANOW CW: Prospective randomized trial of lisuride infusion versus oral levodopa in PD patients. Brain (2002) 125:2058–2066.
  • STOCCHI F, BERARDELLI A, VACCA L et al.: Apomorphine infusion and the long-duration response to levodopa in advanced Parkinson's disease. Clin. Neuropharmacol (2003) 26:151–155.
  • STOCCHI F, BRAMANTE L, MONGE A et al: Apomorphine and lisuride infusion. A comparative chronic study. Adv. Neurol (1993) 60:653–655.
  • STOCCHI F, VACCA L, DEPANDIS MF, BARBATOL L, VALENTE M, RUGGIERI S: Subcutaneous continuous apomorphine infusion in fluctuating patients with Parkinson's disease: long-term results. Neurol Sci. (2001) 22:93–94.
  • MANSON AJ, TURNER K, LEES AJ: Apomorphine monotherapy in the treatment of refractory motor complications of Parkinson's disease: Long-term follow-up study of 64 patients. Mov. Disord. (2002) 17(6):1235–1241.
  • MOURADIAN MM, HEUSER IJ, BARONTI F, CHASE TN: Modification of central dopaminergic mechanisms by continuous levodopa therapy for advanced Parkinson's disease. Ann. Neurol (1990) 27:18-23. A seminal paper presenting for the first time clinical evidence that continuous dopaminergic stimulation can reverse MRCs.
  • MANS ON AJ, HANAGASI H, TURNER K et al.: Intravenous apomorphine therapy in Parkinson's disease: clinical and pharmacokinetic observations. Brain (2001) 124:331–340.
  • WATTS RL, WENDT J, NAUSIEDA PL et al.: Efficacy, safety, and tolerability of the rotigotine transdermal patch in patients with early-stage, idiopathic Parkinson's disease: a multicenter, multinational, randomized, double-blind, placebo-controlled trial. Mov. Disord. (2004) 19\(Suppl. 9):P737.
  • BLINDAUER K, SHOULSON I, KIEBURTZ K et al: A controlled trial of rotigotine monotherapy in early Parkinson's disease. Arch. Neurol (2003) 60 (12):1721–1728.
  • METMAN LV, GILLESPIE M, FARMER C et al: Continuous transdermal dopaminergic stimulation in advanced Parkinson's disease. Clin. Neuropharmacol (2001) 24(3):163–169.
  • •The first clinical noninvasive study to show that continuous dopaminergic stimulation, through a skin patch, can Improve motor fluctuations.
  • BABIC T, BOROOJERDI B, RANDERATH 0, POOLE K, SOMMERVILLE KW: Rotigotine CDS Patch in advanced-stage idiopathic Parkinson's disease: a parallel group, open-label, dose escalation trial. 56th American Academy of Neurology Annual Meeting, San Francisco, CA, USA (2004) P05.095.
  • WOITALLA D, MULLER T, BENZ S, HOROWSKI R, PRZUNTEK H: Transdermal lisuride delivery in the treatment of Parkinson's disease. J. Neural Transm. Suppl. (2004) 68:89–95.
  • CURRAN MP, PERRY CM: Cabergoline: a review of its use in the treatment of Parkinson's disease. Drugs (2004) 64:2125–2141.
  • STEIGER MJ, EL-DEBAS T, ANDERSON T, FINDLEY LJ, MARSDEN CD: Double-blind study of the activity and tolerability of cabergoline versus placebo in Parkinsonains with motor fluctuations. J. Neurol (1996) 243:68–72.
  • CLARKE CE, DEANE KH: Cabergoline for levodopa-induced complications in
  • •• Parkinson's disease. The Cochrane Database of Systematic Reviews (2001) 1:CD001518.
  • MUNGERSDORF M, SOMMER U, SOMMER M et al: High-dose therapy with ropinirole in patients with Parkinson's disease. I Neural Transm. (2001) 108(10:1309–1317.
  • CRISTINA S, ZANGAGLIA R, MAN CINI F, MARTIGNONI E, NAPPI G, PACCHETTI C: High-dose ropinirole in advanced Parkinson's disease with severe dyskinesias. Neuropharmacol (2003) 26(3):146–150.
  • •This study shows that very high doses of a DA agonist can reduce LD-induced dyskinesias.
  • HARDOFF R, TAMIR A, SULA M et al.: Gastric emptying time and gastric motility in patients with Parkinson's disease. Mov. Disord. (2001) 16:104–107.
  • DJALDETTI R, BARON J, ZIV I, MELAMED E: Gastric emptying in Parkinson's disease: patients with and without response fluctuations. Neurology (1996) 46:1051–1054.
  • •A well-designed study on the role of impaired gastric motility in certain forms of motor fluctuations.
  • STOCCHI F, BARBATO L, BRAMANTE L, NORDERA G, VACCA L, RUGGIERI S: Fluctuating Parkinsonism: a pilot study of single afternoon dose of levodopa methyl ester. Neurol (1996) 243:377–380
  • DJALDETTI R, INZELBERG R, GILADI N et al: Oral solution of levodopa ethylester for treatment of response fluctuations in patients with advanced Parkinson's disease. Mov. Disord. (2002) 17:297–302.
  • DJALDETTI R, GILADI N, HASSIN-BAER S, SHABTAI H, MELAMED E: Pharmacokinetics of etilevodopa compared to levodopa in patient's with Parkinson's disease: an open-label, randomized, crossover study. Clin. Neuropharmacol (2003) 26(6):322–326.
  • DI STEFANO A, M CARAFA, P SOZIO et al.: Evaluation of rat striatal L-dopa and DA concentration after intraperitoneal administration of L-dopa prodrugs in liposomal formulations. J. Control. Release (2004) 99(2) 293–300.
  • SUDO J, IWASE H, HIGASHIYAMA K et al.: Elevation of plasma levels of L-dopa in transdermal administration of L-dopa-butylester in rats. Drug. Dev. Ind. Pharm. (2002) 28:59–65.
  • KANKKUNEN T, HUUPPONEN I, LAHTINEN K et al.: Improved stability and release control of levodopa and metaraminol using ion-exchange fibres and transdermal iontophoresis. Eur. Pharm. Sci. (2002) 16(4-5):273–280.
  • KURTH MC, ADLER CH, ST. HILAIRE M et al.: Tolcapone improves motor function and reduces levodopa requirement in patients with Parkinson's disease experiencing motor fluctuations: a multicenter, double-blind, randomized, placebo-controlled trial. Neurology (1997) 48:81–87.
  • ADLER CH, SINGER C, O'BRIEN C et al.: Randomized, placebo-controlled study of tolcapone in patients with fluctuating Parkinson's disease treated with levodopa-carbidopa. Arch. Neurol (1998) 55:1089–1095.
  • PARKINSON STUDY GROUP: Entacapone improves motor fluctuations in levodopa-treated Parkinson's disease patients. Ann. Neurol (1997) 42:747–755.
  • RINNE UK, LARSEN JP, SIDEN A, WORM-PETERSEN J: Entacapone enhances the response to levodopa in Parkinsonian patients with motor fluctuations. NOMECOMT Study Group. Neurology (1998) 51:1309–1314.
  • POEWE WH, DEUSCHL G, GORDIN A, KULTALAHTI ER, LEINOEN M: Efficacy and safety of entacapone in Parkinson's disease patients with suboptimal levodopa response: a 6-month randomized placebo-controlled double-blind study in Germany and Austria (CELOMEN study). Acta Neurol. Scand. (2002) 105:245–255.
  • BROOKS DJ, SAGAR H and the UK-IRISH ENTACAPONE STUDY GROUP: Entacapone is beneficial in both fluctuating and non-fluctuating patients with Parkinson's disease. A randomized, placebo-controlled, double-blind six-month study. Neurol Neurosurg. Psychiatry (2003) 74:1064–1072.
  • JENNER P, AL-BARGHOUTHY G, SMITH L, KNOPPAMAKI M, JACKSON M, ROSES: Entacapone combined with L-dopa enhances antiParkinsonian activity and avoids dyskinesia in the MPTP-treated primate model of Parkinson's disease (PD). Mov. Disord. (2002) 17(5):P146 (Abstract).
  • JENNER P, AL-BARGHOUTHY G, SMITH L et al.: Initiation of entacapone with L-DOPA further improves antiParkinsonian activity and avoids dyskinesia in the MPTP primate model of Parkinson's disease. Neurology (2002) 58(3)374–375.
  • SMITH LA, JACKSON MJ, AL BARGHOUTHY G et al: Multiple small doses of levodopa plus entacapone produces continuous dopaminergic stimulation and reduces dyskinesia induction in MPTP-treated, drug-naive primates. Mov. Disord. (2005) 20(3):388.
  • ••These very interesting studies show that ifLD is administered in combination with entacapone in de novo Parkisonian monkeys, it reduces the induction of dyskinesia.
  • SMITH LA, JACKSON MJ, HANSARD MJ, MARATOS E, JENNER P: Effect of pulsatile administration of L-dopa on dyskinesia induction in drug-naive MPTP-treated common marmosets: effect of dose, frequency of administration, and brain exposure. Mov. Disord. (2003)18:487–495.
  • BONIFACIO MJ, VIEIRA- COELHO MA, SOARES-DA-SILVA P: Kinetic inhibitory profile of BIA 3–202, a novel fast tight-binding, reversible and competitive catechol-O-methyltransferase inhibitor. Eur. Pharmacol (2003) 460(2–3)163–170.
  • LEARMONTH DA, VIEIRA-COELHO MA, BENES J, ALVES PC, BORGES N, FREITAS AP, DA-SILVA PS: Synthesis of 1-(3,4-dihydroxy-5-nitropheny1)-2-phenyl-ethanone and derivatives as potent and long-acting peripheral inhibitors of catechol-0-methyltransferase. Med. Chem. (2002) 45(3):685–95.
  • ALMEIDA L, VAZ-DA-SILVA M, SILVEIRA P: Pharmacokinetic-pharmacodynamic interaction between BIA 3-202, a novel COMT inhibitor, and levodopaicarbidopa. Clin. Neuropharmacol (2004) 27(1):17–24.
  • YOUDIM MB, GROSS A, FINBERG JP:Rasagiline (Npropargy1-1g-)-aminoindan), a selective and potent inhibitor of mitochondrial monoamine oxidase B. Br. J. Pharmacol (2001) 132:500–506.
  • SIDEROWF A, STERN M, SHOULSON I et al: A controlled trial of rasagiline in early Parkinson's disease: the TEMPO Study. Arch. Neurol (2002) 59:1937–1943.
  • RASAGILINE STUDY GROUP: Rasagiline mesylate, a new MAO-B inhibitor for the treatment of Parkinson's disease: a double-blind study as adjunctive therapy to levodopa. Clin. Neurophannacol. (2000) 23(6):324–330.
  • PARKINSON STUDY GROUP: A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson's disease and motor fluctuations: The PRESTO Study. Arch. Neurol. (2005) 62(2):2241–248.
  • RASCOL 0: A comparative randomised study of rasagiline versus placebo or entacapone as adjunct to levodopa in Parkinson's disease patients with motor fluctuations (the LARGO Study). Mov. Disord. (2004) 19\(Suppl. 9):P563.
  • GILADI N: Rasagiline treatment can improve freezing of gait in advanced Parkinson's disease: a prospective randomized, double-blind, placebo and entacapone controlled study. Mov. Disord. (2004) 19(9):P538.
  • STOCCHI F: Effect of rasagiline on severity of OFF in Parkinson's disease. Mov. Disord. (2004) 19(9):P585.
  • HANSARD MJ, SMITH LA, JACKSON MJ, CHEETHAM SC, JENNER P: Dopamine re-uptake inhibition and failure to evoke dyskinesia in MPTP-treated primates. Eur. j Phannacol. (2002) 451(2):157–160.
  • BARA-JIMENEZ W, DIMITROVA T, SHERZAI A et al.: Effect of monoamine re-uptake inhibitor NS 2330 in advanced Parkinson's disease Mov. Disord. (2004) 19(10):1183–1186.
  • BORDET R, RIDRAY S, CARBONI S, DIAZ J, SOKOLOFF P, SCHWARTZ JC: Induction of dopamine D3 receptor expression as a mechanism of behavioural sensitization to levodopa. Proc. Nati Acad. Sci. USA (1997) 94:3363–3367.
  • QUIK M, POLICE S, HE L, DI MONTE DA, LANGSTON JW: Expression of D(3) receptor messenger RNA and binding sites in monkey striatum and substantia nigra after nigrostriatal degeneration: effect of levodopa treatment. Neuroscience (2000) 98:263–273.
  • BEZARD E, FERRY S, MACH U et al.: Attenuation of levodopa induced dyskinesia by normalizing dopamine D3 receptor function. Nat. Med. (2003) 9:762–767.
  • PILLA M, PERACHON S, SAUTEL F et al.: Selective inhibition of cocaine-seeking behaviour by a partial dopamine D3 receptor agonist. Nature (1999) 400:371–375.
  • HSU A, TOGASAKI DM, BEZARD E et al.: Effect of the D3 dopamine receptor partial agonist BP897 (N- [4-(4- [2-methoxyphenyllpiperaziny0 butyll-2-naphthamide) on L-3,4-dihydroxyphenylalanine-induced dyskinesias and Parkinsonism in squirrel monkeys. I Phann. Exp. Therap. (2004) 311:770–777.
  • CHASE TN, OH JD, KONITSIOTIS S: AntiParkinsonian and antidyskinetic activity of drugs targeting central glutamatergic mechanisms. ./. Neurol. (2000) 247(2):36–42.
  • BLANCHET PJ, KONITSIOTIS S, WHITTEMORE ER et al.: Differing effects of N-methl-D-aspartate receptor subtype selective antagonists on dyskinesias in levodopa-treated 1-methy1-4-phenyl-tetrahydropyridine monkeys. I Phannacol. Exp. Ther. (1999) 290(3):1034–1040.
  • •The first study to show that NR2B-selective NMDA antagonists have improved therapeutic profile for LD-induced dyskinesia.
  • PAPA SM, CHASE TN: Levodopa-induced dyskinesias improved by a glutamate antagonist in Parkinsonian monkeys. Ann. Neurol. (1996) 39(5):574–578.
  • NASH JE, FOX SH, HENRY B et al.: AntiParkinsonian actions of ifenprodil in the MPTP-lesioned marmoset model of Parkinson's disease. Exp. Neurol. (2000) 165(1):136–142.
  • MITCHELL IJ, CARROLL CB: Reversal of Parkinsonian symptoms in primates by antagonism of excitatory amino acid transmission: potential mechanisms of action. Neurosci. Biobehav. R. (1997) 21(4):469–475.
  • MARIN C, JIMENEZ A, BONASTRE M et al.: Non-NMDA receptor-mediated mechanisms are involved in levodopa-induced motor response alterations in Parkinsonian rats. Synapse (2000) 36(4):267–274.
  • KONITSIOTIS S, BLANCHET PJ, VERHAGEN L et al.: AMPA receptor blockade improves levodopa-induced dyskinesia in MPTP monkeys. Neurology (2000) 54(8):1589–1595.
  • •The first study to demonstrate that a selective AMPA antagonist reduces LD-induced dyskinesia.
  • MERIMS D, ZIV I, DJALDETTI R et al.: Riluzole for levodopa-induced dyskinesias in advanced Parkinson's disease. Lancet (1999) 353:1764–1765.
  • SHINOTOH H, VINGERHOETS FJG, LEE CS et al.: Lamotrigine trial in idiopathic Parkinsonism: a double-blind, placebo-controlled, crossover study. Neurology (1997) 48:1282–1285.
  • PARKINSON STUDY GROUP: A multicenter randomized controlled trial of remacemide hydrochloride as monotherapy for PD. Neurology (2000) 54:1583–1588.
  • PARKINSON STUDY GROUP: A randomized, controlled trial of remacemide for motor fluctuations in Parkinson's disease. Neurology (2001) 56:455–462.
  • PARKINSON STUDY GROUP: Evaluation of dyskinesias in a pilot, randomized, placebo-controlled trial of remacemide in advanced Parkinson's disease. Arch. Neurol. (2001) 58:1660–1668.
  • VERGAHEN METMAN L, BLANCHET PJ, VAN DEN MUNCKHOF P et al.: A trial of dextromethorphan in Parkinsonian patients with motor response complications. Mov. Disord. (1998) 13:414–417.
  • METMAN LV, DEL DOTTO P, NATTE R et al.: Dextromethorphan improves levodopa-induced dyskinesias in Parkinson's disease. Neurology (1998) 51(1):203–206.
  • MONTASTRUC JL, RASCOL 0, SENARD JM et al.: A pilot study of N-methyl-D-aspartate (NMDA) antagonist in Parkinson's disease../. Neurol. Neurosurg. Psychiatry (1992) 55:630–631.
  • BLANCHET PJ, KONITSIOTIS S, CHASE TN: Amantadine reduces levodopa-induced dyskinesias in Parkinsonian monkeys. Mov. Disord. (1998) 13(5):798–802.
  • METMAN LV, DEL DOTTO P, LEPOOLE K, KONITSIOTIS S, FANG J, CHASE TN: Amantadine for levodopa-induced dyskinesias: a 1-year follow-up study. Arch. Neurol. (1999) 56:1383–1386.
  • RUZICKA E, STREITOVA H, JECH R et al.: Amantadine infusion in treatment of motor fluctuations and dyskinesias in Parkinson's disease../. Neural Transm. (2000) 107:1297–1306.
  • SMITH PF: Therapeutic N-methyl-D-aspartate receptor antagonists: will reality meet expectation? Curr. Opin. Investig. Drugs (2003) 4(7):826–832.
  • WOLLMUTH LP, KUNER T,96.SEEBURG PH, SAKMANN B: Differential contribution of the NR1- and NR2A-subunits to the selectivity filter of recombinant NMDA receptor channels. Physiol (1996) 491:779–797.
  • CHEN Q, REINER A: Cellular distribution of the NMDA receptor NR2A/97.2B subunits in the rat striatum. Brain Res. (1996) 743:346–352.
  • RAYMOND LA, TINGLEY WG, BLACKSTONE CD, ROCHE KW, HUGANIR RL: Glutamate-receptor modulation by protein-phosphorylation.98.Physiol (Paris) (1994) 88:181–192.
  • GURD JW: Protein tyrosine phosphorylation: implications for synaptic function. Neurochern. Int. (1997)31:635–649.
  • SUEN PC, WU K, XU JL, UN SY, LEVINE ES, BLACK IB: NMDA receptor subunits in the postsynaptic density of rat brain: expression and phosphorylation by endogenous protein kinases. Brain Res. Mol Brain Res. (1998) 59:215–228.
  • OH JD, RUSSELL D, VAUGHAN CL, CHASE TN: Enhanced tyrosine phosphorylation of striatal NMDA receptor subunits: Effect of dopaminergic denervation and levodopa administration. Brain Res. (1998) 813:150–159.
  • •Evidence of increased NMDA subunit phosphorylation after chronic LD administration.
  • OH JD, VAUGHAN CL, CHASE TN: Effect of dopamine denervation and dopamine agonist administration on serine phosphorylation of striatal NMDA receptor subunits Brain Res. (1999) 821(2):433–442.
  • •Evidence of increased NMDA subunit102.phosphorylation after chronic LD administration.
  • CALON F, RAJPUT AH, HORNYKIEWICZ 0, BEDARD PJ, DI PAOLO T: Levodopa-induced motor complications are associated with alterations of glutamate receptors in Parkinson's disease. Neurobiol Dis. (2003)103.14(3):404–416.
  • ••This study shows that the upregulation ofNR2B and AMPA glutamate receptors in the striatum was associated with the clinical appearance of LD-induced motor complications in advanced PD patients.104.
  • CHASE TN: Dyskinesias in Parkinson's disease: Molecular mechanisms. Mov. Disord. (2004) 19\(Suppl. 9):037. Parkinson's disease. Mov. Disord. (2003) 18:872–883.
  • NASH JE, BROTCHIE JM: Characterisation of striatal NMDA receptors involved in the generation of Parkinsonian symptoms: intrastriatal microinjection studies in the 6-0HDA-lesioned rat. Mov. Disord. (2002) 17(3):455–466.
  • LOSCHMANN PA, DE GROOTE C, SMITH L et al: AntiParkinsonian activity of Ro 25-6981, a NR2B subunit specific NMDA receptor antagonist, in animal models of Parkinson's disease. Exp. Neurol (2004) 187(1):86–93.
  • HADJ TAHAR A, GREGOIRE L, DARRE A, BELANGER N, MELTZER L, BEDARD PJ: Effect of a selective glutamate antagonist on L-dopa-induced dyskinesias in drug-naive Parkinsonian monkeys. Neurobiol Dis. (2004) 15 (2) :171–176.
  • STEECE-COLLIER K, CHAMBERS LK, JAW-TSAI SS et al.: AntiParkinsonian actions of CP-101,606, an antagonist of NR2B subunit-containing N-methyl-D-aspartate receptors. Exp. Neurol (2000) 163:239–243.
  • WESSELL RH, AHMED SM, MENNITI FS, DUNBAR GL, CHASE TN, OH JD: NR2B selective NMDA receptor antagonist CP-101,606 prevents levodopa-induced motor response alterations in hemi-Parkinsonian rats. Neurophannacology (2004) 47(2):184–94.
  • MERCHANT RE, BULLOCK MR, CARMACK CA et al: A double-blind, placebo-controlled study of the safety, tolerability and pharmacokinetics of CP-101,606 in patients with a mild or moderate traumatic brain injury. Ann. NY Acad. Li. (1999) 890:42–50.
  • SALTARELLI MD, WEAVER JJ, HSU C et al: Randomized double-blind, placebo-controlled study to evaluate the safety and efficacy of CP-101,606 (traxoprodil), an NR2B-selective N-methyl-D-aspartate receptor antagonist, in subjects with acute ischemic stroke. Stroke (2004)35(1):241.
  • TAYLOR TJ, MOULD D, RAVVA P et al: Population pharmacokinetic and pharmacodynamic model of CP-101,606 following a 72-hour infusion in acute ischemic stroke patients. Clin. Pharmacol Ther. (2004) 75(2):97.
  • KOHR G, SEEBURG PH: Subtype-specific regulation of recombinant NMDA receptor-channels by protein tyrosine kinases of the src family. J. Physiol (1996) 492:445–452.
  • •The molecular mechanisms of NMDA receptor functional regulation by protein tyrosine kinases of the Src family.
  • YU XM, ASKALAN R, KEIL GJ, SALTER MW: NMDA channel regulation by channel-associated protein tyrosine kinase Src. Science (1997) 275:674–678.
  • •The molecular mechanisms of NMDA receptor functional regulation by protein tyrosine kinases of the Src family.
  • TAN SE, CHEN SS: The activation of calcium/calmodulin-dependent protein-kinase II after glutamate or potassium stimulation in hippocampal slices. Brain Res. Bull. (1997) 43:269–273.
  • OH JD, DEL DOTTO P, CHASE TN. Protein kinase A inhibitor attenuates levodopa-induced motor response alterations in the hemi-Parkinsonian rat. Neurosci. Lett. (1997) 228:5–8.
  • ••Intracerebral administration of a PKAinhibitor reduces LD-induced motor response complications in Parkinsonian rats.
  • HOLMBERG M, FAGERHOLM V, SCHEININ M: Regional distribution of a(2C)-adrenoceptors in brain and spinal cord of control mice and transgenic mice overexpressing the a(2C)-subtype: an autoradiographic study with ([3]H)RX821002 and ([3]H)rauwolscine. Neuroscience. (2003) 117:875–898.
  • ZHANG W, ORDWAY GA: The a(2C)-adrenoceptor modulates GABA release in mouse striatum. Brain Res. Mol Brain Res. (2003) 112:24–32.
  • HENRY B, FOX SH, PEGGS D et al: The a2-adrenergic receptor antagonist idazoxan reduces dyskinesia and enhances antiParkinsonian actions of levodopa in the MPTP-lesioned primate model of Parkinson's disease. Mov. Disord. (1999) 14:744–753.
  • MANSON AJ, IAKOVIDOU E, LEES AJ: Idazoxan is ineffective for levodopa-induced dyskinesias in Parkinson's disease. Mov. Disord. (2000) 15:336–337.
  • RASCOL 0, ARNULF I, PEYRO-SAINT PH et al: Idazoxan, an (1-2 antagonist, and L-DOPA-induced dyskinesias in patients with Parkinson's disease. Mov. Disord. (2001) 16:708–713.
  • SAVOLA JM, HILL M, ENGSTROM M et al: Fipamezole (JP-1730) is a potent a2-adrenergic receptor antagonist that reduces levodopa-induced dyskinesia in the MPTP-lesioned primate model of
  • •Evidence from Parkinsonian monkeys that a new a2-adrenergic antagonist reduces LD-induced dyskinesia.
  • HILL MP, SAVOLA JM, MERIVOURI H et al.: Potential applications of the a2 adrenergic antagonist, JP-1730, in reducing the problem of L-dopa-induced motor fluctuations in Parkinson's disease: studies in the rodent and primate models of Parkinson's disease. Mov. Disord. (2002) 17\(Suppl. 5):S71.
  • RICHARDSON PJ, KASE H, JENNER PG: Adenosine A2A receptor antagonists as new agents for the treatment of Parkinson's disease. Trends Pharmacol (1997) 18:338–344.
  • •Rationale for the use of A2A adenosine antagonists in PD.
  • MORI A, SHINDOU T, ICHIMURA M, NONAKA H, KASE H: The role of adenosine A2A receptors in regulating GABAergic synaptic transmission in striatal medium spiny neurons. I Neurosci. (1996) 16:605–611.
  • FRANCO R, FERRE S, AGNATI L et al: Evidence for adenosine/dopamine receptor interactions: indications for heteromerization. Neuropsychophannacology (2000) 23:S50–S59.
  • BIBBIANI F, OH JD, PETZER JP et al: A(2A) antagonist prevents dopamine agonist-induced motor complications in animal models of Parkinson's disease. Exp. Neurol (2003) 184(1):285–294.
  • •Evidence from Parkinsonian monkeys that a new a2-adrenergic antagonist reduces LD-induced dyskinesia.
  • KANDA T, JACKSON MJ, SMITH LA et al: Combined use of the adenosine A(2A) antagonist KW-6002 with L-DOPA or with selective D1 or D2 dopamine agonists increases antiParkinsonian activity but not dyskinesia in MPTP-treated monkeys. Exp. Neurol (2000) 162(2):321–327.
  • GRONDIN R, BEDARD PJ, TAHAR AH et al.: AntiParkinsonian effect of a new selective adenosine A(2A) receptor antagonist in MPTP-treated monkeys Neurology (1999) 52(8):1673–1677.
  • KANDA T, JACKSON MJ, SMITH LA et al.: Adenosine A(2A) antagonist: A novel antiParkinsonian agent that does not provoke dyskinesia in Parkinsonian monkeys. Ann. Neurol (1998) 43(4):507–513.
  • •Evidence that the A2A antagonist KW-6002 does not induce, and even prevents, dyskinesia in animal models.
  • HAUSER R, HUBBLE JP, TRUONG DD and the Istradephylline US-001 Study Group: Randomized trial of the adenosine A2A receptor antagonist istradephylline in advanced PD. Neurology (2003) 61:297–303.
  • •Rationale for the use of A2A adenosine antagonists in PD.
  • SHERZAI A, BARA-JIMENEZ W, SHERZAI A, et al: Adenosine A2A antagonist treatment of Parkinson's disease. Neurology (2003) 61:293–296.
  • •The results of the first clinical studies with KW-6002 for MRCs.
  • LEWITT PA: 'Off' time reduction from adjunctive use of istradefylline (KW-6002) in levodopa-treated patients with advanced Parkinson's disease. Mov. Disord. (2004) 19\(Suppl. 9):P624.
  • STACY MA: Istradefylline (KW-6002) as adjunctive therapy in patients with advanced Parkinson's disease: A positive safety profile with supporting efficacy. Mov. Disord. (2004) 19\(Suppl. 9):P605.
  • BEZARD E, BROTCHIE JM, GROSS E: Pathophysiology of levodopa-induced dyskinesia: potential for new therapies. Neuroscience (2001) 2:577–588.
  • MARCO N, THIRION A, MONS G et al.: Activation of dopaminergic and cholinergic neurotransmission by tachykinin NK3 receptor stimulation: an in vivo microdialysis approach in guinea-pig. Neuropeptides (1998) 32:481–488.
  • FUXE K, O'CONNOR WT, ANTONELLI T et al: Evidence for a substrate of neuronal plasticity based on pre and postsynaptic neurotensin-dopamine receptor interactions in the neostriatum. Proc. Natl. Acad. Sci. USA (1992) 89:5591–5595.
  • MANEUF YP, CROSSMAN AR, BROTCHIE JM: Modulation of GABAergic transmission in the globus pallidus by the synthetic cannabinoid WIN 55,212-2. Synapse (1996) 22:382–385.
  • MANEUF YP, NASH JE, CROSSMAN AR, BROTCHIE JM: Activation of the cannabinoid receptor by 8-9-tetrahydrocannabinol reduces y-aminobutyric acid uptake in the globus pallidus. Eur. Phannacol (1996) 308:161–164.
  • BROTCHIE JM: CB1 cannabinoid receptor signalling in Parkinson's disease. Curr. Opin. Phannacol (2003) 3:54–61.
  • •Thorough review on the role of CB receptors in PD.
  • FERRER B, ASBROCK N, KATHURIA S et al: Effects of levodopa on endocannabinoid levels in rat basal ganglia: implications for the treatment of levodopa-induced dyskinesias. Eur. j Neurosci. (2003) 18(6):1607–1614.
  • SEGOVIA G, MORA F, CROSSMAN AR et al: Effects of CBI cannabinoid receptor modulating compounds on the hyperkinesia induced by high-dose levodopa in the reserpine-treated rat model of Parkinson's disease Mov. Disord. (2003) 18(2):138–149.
  • CARROLL CB, BAIN PG, TEARE L et al: Cannabis for dyskinesia in Parkinson's disease: a randomized double-blind crossover study. Neurology (2004) 63(7):1245–1250.
  • •A well-designed study that examined the effects of cannabis on LD-induced dyskinesia.
  • KRONENBERG G, HEUSER I: Randomized, double-blind study of SR142801 (Osanetant), a novel neurokinin-3 (NK3) receptor antagonist in panic disorder with pre and post-treatment cholecystokinin tetrapeptide (CCK-4) challenges. Biol. Psychiat. (2004) 55\(Suppl. 8):443.
  • MOODY TW, CHILES J, CASIBANG MN et al.: 5R48692 is a neurotensin receptor antagonist which inhibits the growth of small cell lung cancer cells Peptides (2001) 22(1):109–115.
  • McCORMICK SE, STOESSL AJ: Central administration of the neurotensin receptor antagonist SR-48692 attenuates vacuous chewing movements in a rodent model of tardive dyskinesia. Neuroscience (2003) 119(2):547–555.
  • HILL M, FOX S, HENRY B et al: The cannabinoid receptor antagonist SR-141716A reduces L-dopa-induced dyskinesia in the MPTP-treated primate model of Parkinson's disease. Eur. Neurosci. (1998) 10\(Suppl. 10):13102.
  • SJOSTROM L, DESPRES JP, GOLAY A: Weight loss in overweight/obese dyslipidemia subjects treated with rimonabant: The RIO-Lipids trial. Int. J. Obesity (2004) 28\(Suppl. 1):528.
  • MESNAGE V, HOUETO JL, BONNET AM et al.: Neurokinin B, neurotensin, and cannabinoid receptor antagonists and Parkinson's disease. Clinical Neuropharmacol (2004) 27(3):108–110.
  • •The first clinical study, although a limited one, on the effects of an NK, a neurotensin and a CB receptor antagonist in PD patients.
  • NICHOLSON SL, BROTCHIE JM: 5-Hydroxytryptamine (5-HT, serotonin) and Parkinson's disease: opportunities for novel therapeutics to reduce the problems of levodopa therapy. Eur. Neurol (2002) 9 (Suppl. 3):1–6.
  • •The rationale for the use of 5-HT-mediated compounds in MRCs.
  • BIBBIANI F, OH JD, CHASE TN: Serotonin 5-HTIA agonist improves motor complications in rodent and primate Parkinsonian models. Neurology (2001) 57: 1829-1834.
  • BARA W, SHERZAI A, BIBBIANI F et al: 5-HTIA agonist effects in advanced Parkinson's disease. Neurology (2003)60:A507.•
  • OLANOW, CW, DAMIER P, GOETZ C et al.: Open-label, trial of Sarizotan in150.Parkinson's disease Patients With Levodopa-Induced Dyskinesias (the SPLENDID Study). Clin. Neuropharmacol (2004) 27(2):58–62.
  • •The results of the first clinical study with•the 5-HTIA agonist sarizotan in PD patients.151.
  • BARTOSZYK GD, VAN AMSTERDAM C, GREINER HE et al: Sarizotan, a serotonin 5-HT 1A receptor agonist and dopamine receptor ligand. 1. Neurochemical profile. I Neural Tranvia. (2004) 111(2):113–126.1c9
  • OH JD, BIBBIANI F, CHASE TN: Quetiapine attenuates levodopa-induced motor complications in rodent and primate Parkinsonian models. Exp. Neurol. (2002) 177:557–564.
  • VANOVER KE, WEINER DM, HARVEY SC et al: ACP-103, a 5-HT2A receptor inverse agonist, a novel potential treatment for psychosis. Schizophr. Res. (2003) 60\(Suppl. 51):317.
  • KLITGAARD H, MATAGNE A, GRIMEE R, VANNESTEGOEMAERE J, MARGINEANU DG: Electrophysiological, neurochemical and regional effects of levetiracetam in the rat pilocarpine model of temporal lobe epilepsy. Seizure (2003) 12:92–100.
  • BEZARD E, HILL MP, CROSSMAN AR et al.: Levetiracetam improves choreic levodopa-induced dyskinesia in the MPTP-treated macaque. Eur. Pharmacol (2004) 485(1-3):159–164.
  • •Studies in Parkinsonian monkeys showing that LEV reduces LD-induced dyskinesia.
  • HILL MP, BEZARD E, McGUIRE S et al.: Novel antiepileptic drug levetiracetam decreases dyskinesia elicited by L-dopa and ropinirole in the MPTP-lesioned marmoset. Mov. Disord. (2003) 18:1301–1305.
  • •Studies in Parkinsonian monkeys showing that LEV reduces LD-induced dyskinesia.
  • HILL M, BROTCHIE J, CROSSMAN A et al: Levetiracetam interferes with the L-Dopa priming process in MPTP-lesioned drug-naive marmosets. Clinical Neuropharmacol (2004) 27(4):171–177.
  • ZESIEWICZ TA, SULLIVAN KL, MALDONADO JL, TAUM WO, HAUSER RA: Levetiracetam in the treatment of levodopa-induced dyskinesia in Parkinson's disease. 56th American Academy of NeurologyAnnual Meeting. (2004)1'06.138.
  • HILL MP, RAVENSCROFT P, BEZARD E: Levetiracetam potentiates the antidyskinetic action of amantadine in the 1-methy1-4-pheny1-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate model of Parkinson's disease. Pharmacol Exp. Ther. (2004) 310(1):386–394.
  • ••Demonstrates that the combined use ofdrugs with different mechanisms of action provides increased clinical benefit with reduced side effects.
  • BIBBIANI F, KIELAITE A, CHASE TN: Combined use of NMDA and AMPA antagonists further reduces levodopa-induced dyskinesias in MPTP-lesioned primates. Mov. Disord. (2004)19\(Suppl. 9):P606.
  • •See ref. 153.
  • LYNCH BA, LAMBENG N, NOCKA K et al.: The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc. Natl. Acad. Sci. USA (2004) 101(26):9861–9866.149.

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