A novel conjugated agent between dopamine and an A 2a adenosine receptor antagonist as a potential anti-Parkinson multitarget approach

Molecular Pharmaceutics

Volumn 9, Issue 3, 2012, Pages 591-604

  Dalpiaz, Alessandro ^a   Cacciari, Barbara ^a   Vicentini, Chiara Beatrice ^a   Bortolotti, Fabrizio ^a   Spalluto, Giampiero ^b   Federico, Stephanie ^b   Pavan, Barbara ^a   Vincenzi, Fabrizio ^a   Borea, Pier Andrea ^a   Varani, Katia ^a  

^a UNIVERSITY OF FERRARA   (Italy)

^b UNIVERSITY OF TRIESTE   (Italy)

Author keywords

A 2A antagonist; A 2A D 2 receptor heteromers; controlled release; dopamine; HPLC; human blood; hydrolysis; prodrug; rat brain homogenates; stability

Indexed keywords

ADENOSINE A2A RECEPTOR; ADENOSINE A2A RECEPTOR ANTAGONIST; ANTIPARKINSON AGENT; DOPAMINE; DOPAMINE 2 RECEPTOR; DOPAMINE DERIVATIVE; TRIAZINE DERIVATIVE; TRIAZOLE DERIVATIVE;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BRAIN HOMOGENATE; CONTROLLED STUDY; CORPUS STRIATUM; DRUG CONJUGATION; DRUG HYDROLYSIS; DRUG RECEPTOR BINDING; DRUG STABILITY; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; MALE; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; RAT; RECEPTOR AFFINITY;

ADENOSINE A2 RECEPTOR ANTAGONISTS; ANIMALS; CHO CELLS; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CORPUS STRIATUM; CRICETINAE; CYCLIC AMP; DOPAMINE; HUMANS; KINETICS; PARKINSONIAN DISORDERS; PRODRUGS; RATS;

EID: 84858045382     PISSN: 15438384     EISSN: 15438392     Source Type: Journal    
DOI: 10.1021/mp200489d     Document Type: Article

References (70)

1. Obeso, J. A.; Rodriguez-Oroz, M. C.; Rodriguez, M.; Lanciego, J.L.; Artrieda, J.; Gonzalo, N.; Olanow, C. W. Pathophysiology of the Basal Ganglia in Parkinson's Disease Trends Neurosci. 2000, 23, S8-S19
2. Djaldetti, R.; Melamed, E. New Therapies for Parkinson's Disease J. Neurol. 2001, 248, 357-362 (Pubitemid 32477325)
3. Olanow, C. W.; Agid, Y.; Mizuno, Y; Albanese, A.; Bonuccelli, U.; Damier, P.; De Yebenes, J.; Gershanik, O.; Guttman, M.; Grandas, F.; Hallett, M.; Hornykiewicz, O.; Jenner, P.; Katzenschlager, R.; Langston, W. J.; LeWitt, P.; Melamed, E.; Mena, M. A.; Michel, P. P.; Mytilineou, C.; Obeso, J. A.; Poewe, W.; Quinn, N.; Raisman-Vozari, R.; Rajput, A. H.; Rascol, O.; Sampaio, C.; Stocchi, F. Levodopa in the Treatment of Parkinson's Disease: Current Controversies Mov. Disord. 2004, 19, 997-1005 (Pubitemid 39302831)
4. Jankovic, J. J. Therapeutic Strategies in Parkinson's disease. In Parkinson's Disease and Movement Disorders; Jankovic, J. J.; Tolosa, E., Eds.; Lippincott Wiliams & Wilkins: Philadelphia, 2002; pp 116-151.
5. Obeso, J. A.; Olanov, C. W.; Nutt, J. G. Levodopa Motor Complications in Parkinson's disease Trends Neurosci. 2000, 23, S2-S7
6. 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 (Pubitemid 36514698)
7. Koller, W. C. Levodopa in the Treatment of Parkinson's Disease Neurology 2000, 55, S2-S7
8. Hattori, N.; Wang, M.; Taka, H.; Fujimura, T.; Yoritaka, A.; Kubo, S.; Mochizuki, H. Toxic Effects of Dopamine Metabolism in Parkinson's Disease Parkinonism Relat. Disord. 2009, 15 (Suppl. 1) S35-S38
9. Yuan, H.; Zhang, Z. W.; Liang, L. W.; Shen, Q.; Wang, X. D.; Ren, S. M.; Ma, H. J.; Jiao, S. J.; Liu, P. Treatment Strategies for Parkinson's Disease Neurosi. Bull. 2010, 26, 66-76
10. 2A Receptor Antagonists and Parkinson's Disease: State of the Art and Future Directions Curr. Pharm. Des. 2008, 14, 1475-1489 (Pubitemid 351997813)
11. Blanchet, P. J.; Calon, F.; Morissette, M.; Tahar, A. H.; Belanger, N.; Samadi, P.; Grondin, R; Grégoire, L.; Meltzer, L.; Di Paolo, T.; Bédard, P. J. Relevance of the MPTP Primate Model in the Study of Dyskinesia Priming Mechanisms Parkinsonism Relat. Disord. 2004, 10, 297-304 (Pubitemid 38757811)
12. Ferré, S.; Ciruela, F.; Woods, A. S.; Liuis, C.; Franco, R. Functional Relevance of Neurotransmitter Receptor Heteromers in the Central Nervous System Trends Neurosci. 2007, 30, 440-446 (Pubitemid 47381459)
13. Fuxe, K; Ferré, S.; Genedani, S.; Franco, R.; Agnati, L. F. Adenosine Receptor-Dopamine Receptor Interactions in the Basal Ganglia and their Relevance for Brain Function Physiol. Behav. 2007, 92, 210-217 (Pubitemid 47381380)
14. Fuxe, K.; Marcellino, D.; Genedani, S.; Agnati, L. Adenosine A(2A) Receptors, Dopamine D(2) Receptors and their Interactions in Parkinson's Disease Mov. Disord. 2007, 22, 1990-2017
15. Antonelli, T.; Fuxe, K.; Agnati, L.; Mazzoni, E.; Tanganelli, S.; Tomasini, M. C.; Ferraro, L. Experimental Studies and Theoretical Aspects on A2A/D2 Receptor Interactions in a Model of Parkinson's Disease. Relevance for L-Dopa Induced Dyskinesias J. Neurol. Sci. 2006, 248, 16-22 (Pubitemid 44647295)
16. Fuxe, K.; Marcellino, D.; Rivera, A.; Diaz-Cabiale, Z.; Filip, M.; Gago, B.; Roberts, D. C.; Lange, U.; Genedani, S.; Ferraro, L.; de la Calle, A.; Narvaez, J.; Tanganelli, S.; Woods, A.; Agnati, L. F. Receptor - Receptor Interactions within Receptor Mosaics. Impact on Neuropsychopharmacology Brain Res. Rev. 2008, 58, 415-452
17. Fuxe, K.; Marcellino, D.; Leo, G.; Agnati, L. F. Molecular Integration Via Allosteric Interactions in Receptor Heteromers. A Working Hypothesis Curr. Opin. Pharmacol. 2010, 10, 14-22
18. Morelli, M.; Wardas., J. Adenosine A(2a) Receptor Antagonists: Potential Therapeutic and Neuroprotective Effects in Parkinson's Disease Neurotoxic. Res. 2001, 3, 545-556 (Pubitemid 33130469)
19. Xu, K.; Bastia, E.; Schwarzschild, M. Therapeutic Potential of Adenosine A(2A) Receptor Antagonists in Parkinson's Disease Pharmacol. Ther. 2005, 105, 267-310 (Pubitemid 40297894)
20. 2A Receptors in Parkinson's Disease Trends Neurosci. 2006, 29, 647-654 (Pubitemid 44602262)
21. Federico, S.; Paoletta, S.; Cheong, S. L.; Pastorin, G.; Cacciari, B.; Stragliotto, S.; Klotz, K. N.; Siegel, J.; Gao, Z. G.; Jacobson, K. A.; Moro, S.; Spalluto, G. Synthesis and Biological Evaluation of a New Series of 1,2,4-Triazolo[1,5-a]-1,3,5-Triazines as Human A2A Adenosine Receptor Antagonists with Improved Water Solubility J. Med. Chem. 2011, 54, 877-889
22. Liu, X.; Yamada, N.; Maruyama, W.; Osawa, T. Formation of Dopamine Adducts Derived from Brain Polyunsaturated Fatty Acids J. Biol. Chem. 2008, 283, 34887-34895
23. 2A Receptor System Using Positron Emission Tomography J. Med. Chem. 2000, 43, 4359-4362 (Pubitemid 32046859)
24. 3 Adenosine Receptors Mol. Pharmacol. 2000, 57, 968-975 (Pubitemid 30253381)
25. 2A Adenosine Receptor Overexpression and Functionality, as well as TNF-α, Correlate with Motor Symptoms in Parkinson's Disease FASEB J. 2010, 24, 587-598
26. 2B Receptors Biochem. Pharmacol. 2005, 70, 1601-1612 (Pubitemid 41540353)
27. Bradford, M. A Rapid and Sensitive Method for the Quantification of Microgram Quantities of Protein Utilizing the Principle of Protein Dye-Binding Anal. Biochem. 1976, 72, 248-254
28. Munson, P. J.; Rodbard, D. Ligand: a Versatile Computerized Approach for the Characterization of Ligand Binding Systems Anal. Biochem. 1980, 107, 220-39
29. Bonina, F.; Puglia, C.; Rimoli, M. G.; Melisi, D.; Boatto, G.; Nieddu, M.; Calignano, A.; La Rana, G.; De Caprariis, P. Glycosyl Derivatives of Dopamine and L-Dopa as Anti-Parkinson Prodrugs: Synthesis, Pharmacological Activity and in Vitro Stability Studies J. Drug Targeting 2003, 11, 25-36 (Pubitemid 36527393)
30. Boison, D. Adenosine as a Neuromodulator in Neurological Diseases Curr. Opin. Pharmacol. 2008, 8, 2-7 (Pubitemid 351168688)
31. Marcellino, D.; Lindqvist, E.; Schneider, M.; Muller, C.; Fuxe, K.; Olson, L.; Galter, D. Chronic A2A Antagonist Treatment Alleviates Parkinsonian Locomotor Deficiency in MitoPark Mice Neurobiol. Dis. 2010, 40, 460-466
32. Knebel, W.; Rao, N.; Uchimura, T.; Mori, A.; Fisher, J.; Gastonguay, M. R.; Chaikin, P. Population Pharmacokinetic Analysis of Istradefylline in Healthy Subjects and in Patients with Parkinson's Disease J. Clin. Pharmacol. 2011, 51, 40-52
33. 2A Receptor Antagonist, is Active in Primate Models of Movement Disorders Exp. Neurol. 2010, 225, 384-390
34. Hauser, R. A.; Cantillon, M.; Pourcher, E.; Micheli, F.; Mok, V.; Onofri, M.; Huyck, S.; Walski, K. Preladenant in Patients with Parkinson's Disease and Motor Fluctuations: a Phase 2, Double-Blind, Randomized Trial Lancet Neurol. 2011, 10, 221-229
35. Fernandez, H. H.; Greeley, D. R.; Zweig, R. M.; Wojcieszek, J.; Mori, A.; Sussman, N. M. 6002-US-051 Study Group. Istradefylline as monotherapy for Parkinson disease: results of the 6002-US-051 trial Parkinsonism Relat. Disord. 2010, 16, 16-20
36. Hauser, R. A. Future treatments for Parkinson's disease: surfing the PD pipeline Int. J. Neurosci. 2011, 121 (Suppl. 2) 53-62
37. 2 Receptor Interactions: Implications For the Function of G-Protein Coupled Receptors Curr. Pharm. Des. 2008, 14, 1468-1474 (Pubitemid 351997812)
38. 2 Heteromeric Receptor Complex and their Function J. Mol. Neurosci. 2005, 26, 209-219 (Pubitemid 41389413)
39. 2A Antagonist SYN115 in Parkinson Disease Neurobiol. Dis. 2010, 30, 16284-16292
40. Sperlágh, B.; Vizi, E. S. The role of extracellular adenosine in chemical neurotransmission in the hippocampus and Basal Ganglia: pharmacological and clinical aspects Curr. Top. Med. Chem. 2011, 11, 1034-1046
41. 1 receptor-mediated inhibition of striatal glutamatergic neurotransmission J. Neurochem. 2011, 116, 273-280
42. 2A receptor interaction in the striatum: implications for Parkinson's disease J. Neurosci. 2011, 31, 1850-1862
43. Westin, J.; Nyholm, D.; Pǎlhagen, S.; Willows, T.; Groth, T.; Dougherty, M.; Karlsson, M. O. A pharmacokinetic-pharmacodynamic model for duodenal levodopa infusion Clin. Neuropharmacol. 2011, 34, 61-65
44. Nyholm, D.; Lewander, T.; Johansson, A.; Lewitt, P. A.; Lundqvist, C.; Aquilonius, S. M. Enteral levodopa/carbidopa infusion in advanced Parkinson disease: long-term exposure Clin. Neuropharmacol. 2008, 31, 63-73 (Pubitemid 351489331)
45. Hauser, R. A.; Ellenbogen, A. L.; Metman, L. V.; Hsu, A.; O'Connell, M. J.; Modi, N. B.; Yao, H. M.; Kell, S. H.; Gupta, S. K. Crossover comparison of IPX066 and a standard levodopa formulation in advanced Parkinson's disease Mov. Disord. 2011, 26, 2246-2252
46. LeWitt, P.; Ellenbogen, A.; Chen, D.; Lal, R.; McGuire, K.; Zomorodi, K.; Lou, W.; Huff, F. J. Actively-transported levodopa prodrug XP21279: a study in Parkinson's disease subjects experiencing motor fluctuation Mov. Disord. 2011, 26 (Suppl. 2) S282
47. Stocchi, F.; Arnold, G.; Onofrj, M.; Kwiecinski, H.; Szczudlik, A.; Thomas, A.; Bonuccelli, U.; Van Dijk, A.; Cattaneo, C.; Sala, P.; Fariello, R. G. Safinamide Parkinson's Study Group. Improvement of motor function in early Parkinson disease by safinamide Neurology 2004, 63, 746-748 (Pubitemid 39100843)
48. Visanji, N. P.; Orsi, A.; Johnston, T. H.; Howson, P. A.; Dixon, K.; Callizot, N.; Brotchie, J. M.; Rees, D. D. PYM50028, a novel, orally active, nonpeptide neurotrophic factor inducer, prevents and reverses neuronal damage induced by MPP+ in mesencephalic neurons and by MPTP in a mouse model of Parkinson's disease FASEB J. 2008, 22, 2488-2497 (Pubitemid 351948666)
49. Grégoire, L.; Morin, N.; Ouattara, B.; Gasparini, F.; Bilbe, G.; Johns, D.; Vranesic, I.; Sahasranaman, S.; Gomez-Mancilla, B.; Di Paolo, T. The acute antiparkinsonian and antidyskinetic effect of AFQ056, a novel metabotropic glutamate receptor type 5 antagonist, in L-Dopa-treated parkinsonian monkeys Parkinsonism Relat. Disord. 2011, 17, 270-276
50. Berg, D.; Godau, J.; Trenkwalder, C.; Eggert, K.; Csoti, I.; Storch, A.; Huber, H.; Morelli-Canelo, M.; Stamelou, M.; Ries, V.; Wolz, M.; Schneider, C.; Di Paolo, T.; Gasparini, F.; Hariry, S.; Vandemeulebroecke, M.; Abi-Saab, W.; Cooke, K.; Johns, D.; Gomez-Mancilla, B. AFQ056 treatment of levodopa-induced dyskinesias: results of 2 randomized controlled trials Mov. Disord. 2011, 26, 1243-1250
51. 2A Receptor Signaling. Relevance for Striatal Function and Parkinson's Disease Neurology 2003, 61 (Suppl. 6) S19-S23
52. 2A Adenosine Receptor Antagonists: a Study on the Importance of Modifications at the Side Chain on the Activity and Solubility J. Med. Chem. 2002, 45, 115-126 (Pubitemid 34038546)
53. 2 Receptor Heteromers J. Med. Chem. 2009, 52, 5590-5602
54. Dalpiaz, A.; Cacciari, B.; Mezzena, M.; Strada, M.; Scalia, S. Solid Lipid Microparticles for the Stability Enhancement of a Dopamine Prodrug J. Pharm. Sci. 2010, 99, 4730-4737
55. Boomsma, F.; Alberts, G.; van Eijk, L. J.; Manin't Veld, A; Schalekamp, M. A. Optimal Collection and Storage Conditions for Catecholamine Measurements in Human Plasma and Urine Clin. Chem. 1993, 39, 2503-2508 (Pubitemid 24008237)
56. Nielsen, N. M.; Bundgaard, H. Evaluation of Glycolamide Esters and Various Other Esters of Aspirin as True Aspirin Prodrugs J. Med. Chem. 1989, 32, 727-734 (Pubitemid 19075734)
57. Dalpiaz, A.; Pavan, B.; Strada, M.; Biondi, C.; Bortolotti, F.; Vertuani, S.; Ciliberti, N; Manfredini, S. Conjugation of Aspirin with Vitamin C: Uptake and Stability Studies J. Drug Delivery Sci. Technol. 2009, 19, 43-50
58. Masson, P.; Froment, M. T.; Fortier, P. L.; Visicchio, J. E.; Bartels, C. F.; Lockridge, O. Butyrylcholinesterase-Catalysed Hydrolysis of Aspirin, a Negatively Charged Ester, and Aspirin-Related Neutral Esters Biochim. Biophys. Acta 1998, 1387, 41-52 (Pubitemid 28529206)
59. Asanuma, M.; Miyazaki, I; Ogawa, N. Dopamine or L-DOPA Induced Neurotoxicity: the Role of Quinone Formation and Tyrosinase in a Model of Parkinson's Disease Neurotoxic. Res. 2003, 5, 165-176
60. Spina, M. B.; Cohen, G. Exposure of School Synaptosomes to L-Dopa Increases Levels of Oxidized Glutatione J. Pharmacol. Exp. Ther. 1988, 247, 502-507
61. Cadet, J. L.; Brannock, C. Free Radicals and the Pathiology of Brain Dopamine Systems Neurochem. Int. 1988, 32, 117-131
62. Golembiowska, K.; Dziubina, A.; Kowalska, M.; Kaminska, K. Paradoxical Effects of Adenosine Receptor Ligands on Hydroxyl Radical Generation by L-DOPA in the Rat Striatum Pharmacol. Rep. 2008, 60, 319-330
63. Hattori, N.; Wang, M.; Taka, H; Fujimura, T.; Yoritaka, A.; Kubo, S.; Mochizuki, H. Toxic Effects of Dopamine Metabolism in Parkinson's Disease Parkinsonism Relat. Disord. 2009, 15 (Suppl. 1) S35-S38
64. Omar, F. A.; Farag, H.; Bodor, N. Synthesis and Evaluation of a Redox Chemical Delivery System for Brain-Enhanced Dopamine Containing an Activated Carbamate-Type Ester J. Drug Targeting 1994, 2, 309-316 (Pubitemid 24351011)
65. Carelli, V.; Liberatore, F.; Scipione, L.; Impicciatore, M.; Barocelli, E.; Cardellini, M.; Giorgioni, G. New Systems for the Specific Delivery and Sustained Release of Dopamine to the Brain J. Controlled Release 1996, 42, 209-216 (Pubitemid 26338596)
66. Prokai, L.; Prokai-Tatrai, K.; Bodor, N. Targeting Drugs to the Brain by Redox Chemical Delivery Systems Med. Res. Rev. 2000, 20, 367-416
67. Illum, L. Is Nose-to-Brain Transport of Drugs in Man a Reality? J. Pharm. Pharmacol. 2004, 56, 3-17 (Pubitemid 38195323)
68. Hanson, L. R.; Frey, W. H., II. Strategies for Intranasal Delivery of Therapeutics for the Prevention and Treatment of NeuroAIDS J. Neuroimmune Pharmacol. 2007, 2, 81-86
69. Dalpiaz, A.; Gavini, E.; Colombo, G.; Russo, P.; Bortolotti, F.; Ferraro, L.; Tanganelli, S.; Scatturin, A.; Menegatti, E.; Giunchedi, P. Brain Uptake of an Antiischemic Agent by Nasal Administration of Microparticles J. Pharm. Sci. 2008, 97 (11) 4889-4903
70. Gavini, E.; Rassu, G.; Ferraro, L.; Generosi, A.; Rau, J. V.; Brunetti, A.; Giunchedi, P.; Dalpiaz, A. Influence of Chitosan Glutamate on the in Vivo Intranasal Absorption of Rokitamycin from Microspheres J. Pharm. Sci. 2011, 100, 1488-1502