A mGluR5 antagonist under clinical development improves L-DOPA-induced dyskinesia in parkinsonian rats and monkeys

Neurobiology of Disease

Volumn 39, Issue 3, 2010, Pages 352-361

  Rylander, Daniella ^a   Iderberg, Hanna ^a   Li, Qin ^b,c   Dekundy, Andrzej ^d   Zhang, Jinlan ^e   Li, Hao ^b,c   Baishen, Ren ^b,c   Danysz, Wojciech ^d   Bezard, Erwan ^b,c   Cenci, M Angela ^a  

^a LUND UNIVERSITY   (Sweden)

^b INSTITUTE OF LABORATORY ANIMAL SCIENCE   (China)

^c UNIVERSITÉ DE BORDEAUX   (France)

^d MERZ PHARMACEUTICALS GMBH   (Germany)

^e INSTITUTE OF MATERIA MEDICA   (China)

Author keywords

AIMs; Dopamine denervation; Dopamine replacement; Glutamate receptor; Involuntary movements; LID; MGluR; Motor complication; Neurotransmitter; Rotarod; Rotation; Striatum

Indexed keywords

1,2,3,6 TETRAHYDRO 1 METHYL 4 PHENYLPYRIDINE; AMANTADINE; BENSERAZIDE PLUS LEVODOPA; CARBIDOPA PLUS LEVODOPA; FENOBAM; LEVODOPA; METABOTROPIC RECEPTOR 5; METABOTROPIC RECEPTOR ANTAGONIST; UNCLASSIFIED DRUG;

ANIMAL BEHAVIOR; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DRUG ACTIVITY; DRUG BLOOD LEVEL; DRUG CEREBROSPINAL FLUID LEVEL; DRUG DOSE INCREASE; DYSKINESIA; FEMALE; LOCOMOTION; MALE; MONKEY; NONHUMAN; PARKINSON DISEASE; PARKINSONISM; PRIORITY JOURNAL; RAT; SCORING SYSTEM;

EID: 77954956744     PISSN: 09699961     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.nbd.2010.05.001     Document Type: Article

References (70)

1. Aguirre J.A., Kehr J., Yoshitake T., Liu F.L., Rivera A., Fernandez-Espinola S., Andbjer B., Leo G., Medhurst A.D., Agnati L.F., Fuxe K. Protection but maintained dysfunction of nigral dopaminergic nerve cell bodies and striatal dopaminergic terminals in MPTP-lesioned mice after acute treatment with the mGluR5 antagonist MPEP. Brain Res. 2005, 1033:216-220.
2. Armentero M.T., Fancellu R., Nappi G., Bramanti P., Blandini F. Prolonged blockade of NMDA or mGluR5 glutamate receptors reduces nigrostriatal degeneration while inducing selective metabolic changes in the basal ganglia circuitry in a rodent model of Parkinson's disease. Neurobiol. Dis. 2006, 22:1-9.
3. Aubert I., Guigoni C., Hakansson K., Li Q., Dovero S., Barthe N., Bioulac B.H., Gross C.E., Fisone G., Bloch B., Bezard E. Increased D1 dopamine receptor signaling in levodopa-induced dyskinesia. Ann. Neurol. 2005, 57:17-26.
4. Berry-Kravis E., Hessl D., Coffey S., Hervey C., Schneider A., Yuhas J., Hutchison J., Snape M., Tranfaglia M., Nguyen D.V., Hagerman R. A pilot open label, single dose trial of fenobam in adults with fragile X syndrome. J. Med. Genet. 2009, 46:266-271.
5. Berthet A., Bezard E. Dopamine receptors and L-dopa-induced dyskinesia. Parkinsonism Relat. Disord. 2009, 15(Suppl 4):S8-S12.
6. Berton O., Guigoni C., Li Q., Bioulac B.H., Aubert I., Gross C.E., Dileone R.J., Nestler E.J., Bezard E. Striatal overexpression of DeltaJunD resets L-DOPA-induced dyskinesia in a primate model of Parkinson disease. Biol. Psychiatry 2009, 66:554-561.
7. Bezard E., Brotchie J.M., Gross C.E. Pathophysiology of levodopa-induced dyskinesia: potential for new therapies. Nat. Rev. Neurosci. 2001, 2:577-588.
8. Bezard E., Dovero S., Prunier C., Ravenscroft P., Chalon S., Guilloteau D., Crossman A.R., Bioulac B., Brotchie J.M., Gross C.E. Relationship between the appearance of symptoms and the level of nigrostriatal degeneration in a progressive 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-lesioned macaque model of Parkinson's disease. J. Neurosci. 2001, 21:6853-6861.
9. Bezard E., Ferry S., Mach U., Stark H., Leriche L., Boraud T., Gross C., Sokoloff P. Attenuation of levodopa-induced dyskinesia by normalizing dopamine D3 receptor function. Nat. Med. 2003, 9:762-767.
10. Bezard E., Gross C.E., Qin L., Gurevich V.V., Benovic J.L., Gurevich E.V. L-DOPA reverses the MPTP-induced elevation of the arrestin2 and GRK6 expression and enhanced ERK activation in monkey brain. Neurobiol. Dis. 2005, 18:323-335.
11. Breysse N., Amalric M., Salin P. Metabotropic glutamate 5 receptor blockade alleviates akinesia by normalizing activity of selective basal-ganglia structures in parkinsonian rats. J. Neurosci. 2003, 23:8302-8309.
12. Bruno V., Copani A., Knopfel T., Kuhn R., Casabona G., Dell'Albani P., Condorelli D.F., Nicoletti F. Activation of metabotropic glutamate receptors coupled to inositol phospholipid hydrolysis amplifies NMDA-induced neuronal degeneration in cultured cortical cells. Neuropharmacology 1995, 34:1089-1098.
13. Busse C.S., Brodkin J., Tattersall D., Anderson J.J., Warren N., Tehrani L., Bristow L.J., Varney M.A., Cosford N.D. The behavioral profile of the potent and selective mGlu5 receptor antagonist 3-[(2-methyl-1, 3-thiazol-4-yl)ethynyl]pyridine (MTEP) in rodent models of anxiety. Neuropsychopharmacology 2004, 29:1971-1979.
14. Calabresi P., Picconi B., Tozzi A., Di Filippo M. Dopamine-mediated regulation of corticostriatal synaptic plasticity. Trends Neurosci. 2007, 30:211-219.
15. Carta M., Lindgren H.S., Lundblad M., Stancampiano R., Fadda F., Cenci M.A. Role of striatal L-DOPA in the production of dyskinesia in 6-hydroxydopamine lesioned rats. J. Neurochem. 2006, 96:1718-1727.
16. Cenci M.A. Dopamine dysregulation of movement control in L-DOPA-induced dyskinesia. Trends Neurosci. 2007, 30:236-243.
17. Cenci M.A., Lindgren H.S. Advances in understanding L-DOPA-induced dyskinesia. Curr. Opin. Neurobiol. 2007, 17:665-671.
18. Cenci M.A., Lundblad M. Post- versus presynaptic plasticity in L-DOPA-induced dyskinesia. J. Neurochem. 2006, 99:381-392.
19. Cenci M.A., Lundblad M. Ratings of L-DOPA-induced dyskinesia in the unilateral 6-OHDA lesion model of Parkinson's disease in rats and mice. Curr. Protoc Neurosci. Chapter 2007, 9(Unit 9):25.
20. Chase T.N., Oh J.D. Striatal dopamine- and glutamate-mediated dysregulation in experimental parkinsonism. Trends Neurosci. 2000, 23:S86-S91.
21. Chase T.N., Oh J.D., Konitsiotis S. Antiparkinsonian and antidyskinetic activity of drugs targeting central glutamatergic mechanisms. J. Neurol. 2000, 247(Suppl 2):II36-II42.
22. Conn P.J., Battaglia G., Marino M.J., Nicoletti F. Metabotropic glutamate receptors in the basal ganglia motor circuit. Nat. Rev. Neurosci. 2005, 6:787-798.
23. Dekundy A., Pietraszek M., Schaefer D., Cenci M.A., Danysz W. Effects of group I metabotropic glutamate receptors blockade in experimental models of Parkinson's disease. Brain Res. Bull. 2006, 69:318-326.
24. Fabbrini G., Brotchie J.M., Grandas F., Nomoto M., Goetz C.G. Levodopa-induced dyskinesias. Mov. Disord. 2007, 22:1379-1389. quiz 1523.
25. Fox S.H., Brotchie J.M., Lang A.E. Non-dopaminergic treatments in development for Parkinson's disease. Lancet Neurol. 2008, 7:927-938.
26. Fox S.H., Lang A.E., Brotchie J.M. Translation of nondopaminergic treatments for levodopa-induced dyskinesia from MPTP-lesioned nonhuman primates to phase IIa clinical studies: keys to success and roads to failure. Mov. Disord. 2006, 21:1578-1594.
27. Gardoni F., Picconi B., Ghiglieri V., Polli F., Bagetta V., Bernardi G., Cattabeni F., Di Luca M., Calabresi P. A critical interaction between NR2B and MAGUK in L-DOPA induced dyskinesia. J. Neurosci. 2006, 26:2914-2922.
28. Gasparini F., Lingenhohl K., Stoehr N., Flor P.J., Heinrich M., Vranesic I., Biollaz M., Allgeier H., Heckendorn R., Urwyler S., Varney M.A., Johnson E.C., Hess S.D., Rao S.P., Sacaan A.I., Santori E.M., Velicelebi G., Kuhn R. 2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist. Neuropharmacology 1999, 38:1493-1503.
29. Gerfen C.R. The neostriatal mosaic: multiple levels of compartmental organization. J. Neural Transm. Suppl. 1992, 36:43-59.
30. Gold S.J., Hoang C.V., Potts B.W., Porras G., Pioli E., Kim K.W., Nadjar A., Qin C., LaHoste G.J., Li Q., Bioulac B.H., Waugh J.L., Gurevich E., Neve R.L., Bezard E. RGS9-2 negatively modulates L-3, 4-dihydroxyphenylalanine-induced dyskinesia in experimental Parkinson's disease. J. Neurosci. 2007, 27:14338-14348.
31. Gubellini P., Pisani A., Centonze D., Bernardi G., Calabresi P. Metabotropic glutamate receptors and striatal synaptic plasticity: implications for neurological diseases. Prog. Neurobiol. 2004, 74:271-300.
32. Guigoni C., Dovero S., Aubert I., Li Q., Bioulac B.H., Bloch B., Gurevich E.V., Gross C.E., Bezard E. Levodopa-induced dyskinesia in MPTP-treated macaques is not dependent on the extent and pattern of nigrostrial lesioning. Eur. J. Neurosci. 2005, 22:283-287.
33. Hallett P.J., Dunah A.W., Ravenscroft P., Zhou S., Bezard E., Crossman A.R., Brotchie J.M., Standaert D.G. Alterations of striatal NMDA receptor subunits associated with the development of dyskinesia in the MPTP-lesioned primate model of Parkinson's disease. Neuropharmacology 2005, 48:503-516.
34. Jacob W., Gravius A., Pietraszek M., Nagel J., Belozertseva I., Shekunova E., Malyshkin A., Greco S., Barberi C., Danysz W. The anxiolytic and analgesic properties of fenobam, a potent mGlu5 receptor antagonist, in relation to the impairment of learning. Neuropharmacology 2009, 57:97-108.
35. Jimenez A., Bonastre M., Aguilar E., Marin C. Effect of the metabotropic glutamate antagonist MPEP on striatal expression of the Homer family proteins in levodopa-treated hemiparkinsonian rats. Psychopharmacology (Berl) 2009, 206:233-242.
36. Konradi C., Westin J.E., Carta M., Eaton M.E., Kuter K., Dekundy A., Lundblad M., Cenci M.A. Transcriptome analysis in a rat model of L-DOPA-induced dyskinesia. Neurobiol. Dis. 2004, 17:219-236.
37. Levandis G., Bazzini E., Armentero M.T., Nappi G., Blandini F. Systemic administration of an mGluR5 antagonist, but not unilateral subthalamic lesion, counteracts l-DOPA-induced dyskinesias in a rodent model of Parkinson's disease. Neurobiol. Dis. 2008, 29:161-168.
38. Lindgren H.S., Andersson D.R., Lagerkvist S., Nissbrandt H., Cenci M.A. l-DOPA-induced dopamine efflux in the striatum and the substantia nigra in a rat model of Parkinson's disease: temporal and quantitative relationship to the expression of dyskinesia. J. Neurochem. 2010, 112:1465-1476.
39. Loscher W., Dekundy A., Nagel J., Danysz W., Parsons C.G., Potschka H. mGlu1 and mGlu5 receptor antagonists lack anticonvulsant efficacy in rodent models of difficult-to-treat partial epilepsy. Neuropharmacology 2006, 50:1006-1015.
40. Lundblad M., Andersson M., Winkler C., Kirik D., Wierup N., Cenci M.A. Pharmacological validation of behavioural measures of akinesia and dyskinesia in a rat model of Parkinson's disease. Eur. J. Neurosci. 2002, 15:120-132.
41. Lundblad M., Vaudano E., Cenci M.A. Cellular and behavioural effects of the adenosine A2a receptor antagonist KW-6002 in a rat model of l-DOPA-induced dyskinesia. J. Neurochem. 2003, 84:1398-1410.
42. Mao L.M., Zhang G.C., Liu X.Y., Fibuch E.E., Wang J.Q. Group I metabotropic glutamate receptor-mediated gene expression in striatal neurons. Neurochem. Res. 2008, 33:1920-1924.
43. Mares P. Age-dependent anticonvulsant action of antagonists of group I glutamate metabotropic receptors in rats. Epilepsy Res. 2009, 83:215-223.
44. Marino M.J., Conn P.J. Glutamate-based therapeutic approaches: allosteric modulators of metabotropic glutamate receptors. Curr. Opin. Pharmacol. 2006, 6:98-102.
45. Mela F., Marti M., Dekundy A., Danysz W., Morari M., Cenci M.A. Antagonism of metabotropic glutamate receptor type 5 attenuates l-DOPA-induced dyskinesia and its molecular and neurochemical correlates in a rat model of Parkinson's disease. J. Neurochem. 2007, 101:483-497.
46. Meldrum B.S. The glutamate synapse as a therapeutical target: perspectives for the future. Prog. Brain Res. 1998, 116:441-458.
47. Miller S., Kesslak J.P., Romano C., Cotman C.W. Roles of metabotropic glutamate receptors in brain plasticity and pathology. Ann. N Y Acad. Sci. 1995, 757:460-474.
48. Montana M.C., Cavallone L.F., Stubbert K.K., Stefanescu A.D., Kharasch E.D., Gereau R.W.t. The metabotropic glutamate receptor subtype 5 antagonist fenobam is analgesic and has improved in vivo selectivity compared with the L prototypical antagonist 2-methyl-6-(phenylethynyl)-pyridine. J. Pharmacol. Exp. Ther. 2009, 330:834-843.
49. Morin N., Gregoire L., Gomez-Mancilla B., Gasparini F., Di Paolo T. Effect of the metabotropic glutamate receptor type 5 antagonists MPEP and MTEP in parkinsonian monkeys. Neuropharmacology 2010, 58:981-986.
50. Morrish P.K., Sawle G.V., Brooks D.J. An [18F]dopa-PET and clinical study of the rate of progression in Parkinson's disease. Brain 1996, 119(Pt 2):585-591.
51. Munoz A., Li Q., Gardoni F., Marcello E., Qin C., Carlsson T., Kirik D., Di Luca M., Bjorklund A., Bezard E., Carta M. Combined 5-HT1A and 5-HT1B receptor agonists for the treatment of L-DOPA-induced dyskinesia. Brain 2008, 131:3380-3394.
52. Nadjar A., Gerfen C.R., Bezard E. Priming for l-dopa-induced dyskinesia in Parkinson's disease: a feature inherent to the treatment or the disease?. Prog. Neurobiol. 2009, 87:1-9.
53. Ouattara, B., Gregoire, L., Morissette, M., Gasparini, F., Vranesic, I., Bilbe, G., Johns, D.R., Rajput, A., Hornykiewicz, O., Rajput, A.H., Gomez-Mancilla, B., Di Paolo, T., in press. Metabotropic glutamate receptor type 5 in levodopa-induced motor complications. Neurobiol. Aging doi:10.1016/j.neurobiolaging.2009.07.014.
54. Pecknold J.C., McClure D.J., Appeltauer L., Wrzesinski L., Allan T. Treatment of anxiety using fenobam (a nonbenzodiazepine) in a double-blind standard (diazepam) placebo-controlled study. J. Clin. Psychopharmacol. 1982, 2:129-133.
55. Picconi B., Centonze D., Hakansson K., Bernardi G., Greengard P., Fisone G., Cenci M.A., Calabresi P. Loss of bidirectional striatal synaptic plasticity in L-DOPA-induced dyskinesia. Nat. Neurosci. 2003, 6:501-506.
56. Pin J.P., Duvoisin R. The metabotropic glutamate receptors: structure and functions. Neuropharmacology 1995, 34:1-26.
57. Pisani A., Gubellini P., Bonsi P., Conquet F., Picconi B., Centonze D., Bernardi G., Calabresi P. Metabotropic glutamate receptor 5 mediates the potentiation of N-methyl-d-aspartate responses in medium spiny striatal neurons. Neuroscience 2001, 106:579-587.
58. Porter R.H., Jaeschke G., Spooren W., Ballard T.M., Buttelmann B., Kolczewski S., Peters J.U., Prinssen E., Wichmann J., Vieira E., Muhlemann A., Gatti S., Mutel V., Malherbe P. Fenobam: a clinically validated nonbenzodiazepine anxiolytic is a potent, selective, and noncompetitive mGlu5 receptor antagonist with inverse agonist activity. J. Pharmacol. Exp. Ther. 2005, 315:711-721.
59. Robelet S., Melon C., Guillet B., Salin P., Kerkerian-Le Goff L. Chronic L-DOPA treatment increases extracellular glutamate levels and GLT1 expression in the basal ganglia in a rat model of Parkinson's disease. Eur. J. Neurosci. 2004, 20:1255-1266.
60. Rouse S.T., Marino M.J., Bradley S.R., Awad H., Wittmann M., Conn P.J. Distribution and roles of metabotropic glutamate receptors in the basal ganglia motor circuit: implications for treatment of Parkinson's disease and related disorders. Pharmacol. Ther. 2000, 88:427-435.
61. Rylander D., Recchia A., Mela F., Dekundy A., Danysz W., Cenci M.A. Pharmacological modulation of glutamate transmission in a rat model of L-DOPA-induced dyskinesia: effects on motor behavior and striatal nuclear signaling. J. Pharmacol. Exp. Ther. 2009, 330:227-235.
62. Samadi P., Gregoire L., Morissette M., Calon F., Hadj Tahar A., Belanger N., Dridi M., Bedard P.J., Di Paolo T. Basal ganglia group II metabotropic glutamate receptors specific binding in non-human primate model of L-Dopa-induced dyskinesias. Neuropharmacology 2008, 54:258-268.
63. Santini E., Valjent E., Usiello A., Carta M., Borgkvist A., Girault J.A., Herve D., Greengard P., Fisone G. Critical involvement of cAMP/DARPP-32 and extracellular signal-regulated protein kinase signaling in L-DOPA-induced dyskinesia. J. Neurosci. 2007, 27:6995-7005.
64. Silverdale M.A., Kobylecki C., Hallett P.J., Li Q., Dunah A.W., Ravenscroft P., Bezard E., Brotchie J.M. Synaptic recruitment of AMPA glutamate receptor subunits in levodopa-induced dyskinesia in the MPTP-lesioned nonhuman primate. Synapse 2010, 64:177-180.
65. Spooren W.P., Gasparini F., Bergmann R., Kuhn R. Effects of the prototypical mGlu(5) receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine on rotarod, locomotor activity and rotational responses in unilateral 6-OHDA-lesioned rats. Eur. J. Pharmacol. 2000, 406:403-410.
66. Spooren W.P., Vassout A., Neijt H.C., Kuhn R., Gasparini F., Roux S., Porsolt R.D., Gentsch C. Anxiolytic-like effects of the prototypical metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)pyridine in rodents. J. Pharmacol. Exp. Ther. 2000, 295:1267-1275.
67. Testa C.M., Standaert D.G., Young A.B., Penney J.B. Metabotropic glutamate receptor mRNA expression in the basal ganglia of the rat. J. Neurosci. 1994, 14:3005-3018.
68. Voulalas P.J., Holtzclaw L., Wolstenholme J., Russell J.T., Hyman S.E. Metabotropic glutamate receptors and dopamine receptors cooperate to enhance extracellular signal-regulated kinase phosphorylation in striatal neurons. J. Neurosci. 2005, 25:3763-3773.
69. Westin J.E., Vercammen L., Strome E.M., Konradi C., Cenci M.A. Spatiotemporal pattern of striatal ERK1/2 phosphorylation in a rat model of L-DOPA-induced dyskinesia and the role of dopamine D1 receptors. Biol. Psychiatry 2007, 62:800-810.
70. Yamamoto N., Soghomonian J.J. Metabotropic glutamate mGluR5 receptor blockade opposes abnormal involuntary movements and the increases in glutamic acid decarboxylase mRNA levels induced by l-DOPA in striatal neurons of 6-hydroxydopamine-lesioned rats. Neuroscience 2009, 163:1171-1180.