Subtype-selective dopamine receptor radioligands for PET imaging: Current status and recent developments

Current Medicinal Chemistry

Volumn 19, Issue 23, 2012, Pages 3957-3966

  Banerjee, A ^a   Prante, O ^a  

^a UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

Author keywords

C 11; D2; D3; D4; Dopamine; Dopamine receptor; F 18; PET; PET ligand; Positron emission tomography; Radioligand; Radiopharmaceutical; Selectivity; Subtype selectivity

Indexed keywords

1 (2 BROMO 4,5 DIMETHOXYBENZYL) 1,2,3,4 TETRAHYDRO 7 HYDROXY 6 METHOXY 2 METHYLISOQUINOLINE C 11; 2 DIPROPYLAMINO 5 METHOXY 1 METHYLTETRALIN C 11; 3 CHLORO 5 ETHYL 6 HYDROXYN ((1 METHYL 2 PYRROLIDINYL)METHYL) O ANISAMIDE C 11; 3 METHYLSPIPERONE C 11; 5 (2,3 DIHYDROBENZOFURAN 7 YL) 2,3,4,5 TETRAHYDRO 3 METHYL 8 NITRO 1H 3 BENZAZEPIN 7 OL C 11; 5 (7 BENZOFURANYL) 8 CHLORO 2,3,4,5 TETRAHYDRO 7 HYDROXY 3 METHYL 1H 3 BENZAZEPINE C 11; 8 CHLORO 2,3,4,5 TETRAHYDRO 3 METHYL 5 PHENYL 1H 3 BENZAZEPIN 7 OL HYDROGEN MALEATE C 11; BENPERIDOL F 18; BERUPIPAM C 11; BP 897 C 11; BROMOSPIPERONE BR 76; CARBON 11; DOPAMINE 1 RECEPTOR; DOPAMINE 2 RECEPTOR; DOPAMINE 3 RECEPTOR; DOPAMINE 4 RECEPTOR; ECOPIPAM C 11; ETICLOPRID C 11; FALLYPRIDE F 18; FLUORODEOXYGLUCOSE F 18; FLUOROPROPYLEPIDEPRIDE F 18; KETANSERIN; LORAZEPAM; METHIOPROPRAMINE C 11; METHYL IODIDE C 11; N FLUOROPROPYL SPIPERONE F 18; NEUROLEPTIC AGENT; RACLOPRIDE C 11; RADIOPHARMACEUTICAL AGENT; UNCLASSIFIED DRUG; UNINDEXED DRUG;

BASAL GANGLION; BINDING AFFINITY; BINDING KINETICS; BRAIN CORTEX; CEREBELLUM; CHEMICAL STRUCTURE; CORPUS STRIATUM; DOPAMINE RELEASE; DOPAMINERGIC SYSTEM; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG SELECTIVITY; DRUG UPTAKE; HUMAN; IN VITRO STUDY; IN VIVO STUDY; ISOTOPE LABELING; LIGAND BINDING; MENTAL PERFORMANCE; NEOCORTEX; NONHUMAN; PARKINSON DISEASE; POSITRON EMISSION TOMOGRAPHY; PREMEDICATION; PROTEIN EXPRESSION; RADIOACTIVITY; REVIEW; THALAMUS;

BRAIN; HUMANS; LIGANDS; POSITRON-EMISSION TOMOGRAPHY; PROTEIN ISOFORMS; RADIOPHARMACEUTICALS; RECEPTORS, DOPAMINE;

EID: 84865735142     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/092986712802002518     Document Type: Review

References (101)

1. Neve, K.A., The Dopamine Receptors. Humana Press: New York, 2010.
2. Fremeau, R.T., Jr.; Duncan, G.E.; Fornaretto, M.G.; Dearry, A.; Gingrich, J.A.; Breese, G.R.; Caron, M.G. Localization of D1 dopamine receptor mRNA in brain supports a role in cognitive, affective, and neuroendocrine aspects of dopaminergic neurotransmission. Proc. Natl. Acad. Sci. U. S. A. 1991, 88, 3772-6. (Pubitemid 21916706)
3. Joyce, J.N.; Meador-Woodruff, J.H. Linking the family of D2 receptors to neuronal circuits in human brain: insights into schizophrenia. Neuropsychopharmacology 1997, 16, 375-84. (Pubitemid 27244443)
4. Pilla, M.; Perachon, S.; Sautel, F.; Garrido, F.; Mann, A.; Wermuth, C.G.; Schwartz, J.C.; Everitt, B.J.; Sokoloff, P. Selective inhibition of cocaineseeking behaviour by a partial dopamine D3 receptor agonist. Nature 1999, 400, 371-5. (Pubitemid 29344203)
5. Caine, S.B.; Koob, G.F. Modulation of cocaine self-administration in the rat through D-3 dopamine receptors. Science 1993, 260, 1814-6.
6. Kapur, S.; Zipursky, R.; Jones, C.; Shammi, C.S.; Remington, G.; Seeman, P. A positron emission tomography study of quetiapine in schizophrenia: a preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy. Arch. Gen. Psychiatry 2000, 57, 553-9. (Pubitemid 30349435)
7. Schmidt, B.; Braun, H.A.; Narlawar, R. Drug development and PETdiagnostics for Alzheimer's disease. Curr. Med. Chem. 2005, 12, 1677-1695. (Pubitemid 40895008)
8. Kopka, K.; Law, M.P.; Breyholz, H.J.; Faust, A.; Hoeltke, C.; Riemann, B.; Schober, O.; Schaefers, M.; Wagner, S. Non-invasive molecular imaging of β-adrenoceptors In vivo: Perspectives for PET-radioligands. Curr. Med. Chem. 2005, 12, 2057-2074. (Pubitemid 41086748)
9. Zouhair, A.; Ozsahin, M.; Schaffer, M.; Albrecht, S.; Camus, F.; Jichlinski, P.; Mirimanoff, R.O.; Delaloye, A.B.; Meuwly, J.Y.; Prior, J.O. Positron emission tomography and computer tomography (PET/CT) in prostate, bladder, and testicular cancers. Curr. Med. Chem. 2010, 17, 2492-2502.
10. 11C]raclopride with ultrahigh specific activity in rat brain determined by homogenate assay and autoradiography. Nucl. Med. Biol. 2008, 35, 19-27. (Pubitemid 350298250)
11. Hyttel, J. SCH 23390 -the first selective dopamine D-1 antagonist. Eur. J. Pharmacol. 1983, 91, 153-4. (Pubitemid 13079000)
12. Friedman, A.M.; Dejesus, O.T.; Woolverton, W.L.; Van Moffaert, G.; Goldberg, L.I.; Prasad, A.; Barnett, A.; Dinerstein, R.J. Positron tomography of a radio-brominated analog of the D1/DA1 antagonist, SCH 23390. Eur. J. Pharmacol. 1985, 108, 327-8. (Pubitemid 15130328)
13. Halldin, C.; Stone-Elander, S.; Farde, L.; Ehrin, E.; Fasth, K.J.; Laangstroem, B.; Sedvall, G. Preparation of carbon-11-labelled SCH 23390 for the in vivo study of dopamine D-1 receptors using positron emission tomography. Appl. Radiat. Isot. 1986, 37, 1039-43.
14. Halldin, C.; Farde, L.; Barnett, A.; Sedvall, G. Synthesis of carbon-11 labeled SCH 39166, a new selective dopamine D-1 receptor ligand, and preliminary PET investigations. Appl. Radiat. Isot. 1991, 42, 451-5.
15. 11C]NNC 756, dopamine D-1 receptor ligands. Preparation, autoradiography and PET investigation in monkey. Nucl. Med. Biol. 1993, 20, 945-53. (Pubitemid 23338078)
16. Laihinen, A.O.; Rinne, J.O.; Ruottinen, H.M.; Nagren, K.A.; Lehikoinen, P.K.; Oikonen, V.J.; Ruotsalainen, U.H.; Rinne, U.K. PET studies on dopamine D1 receptors in the human brain with carbon-11-SCH 39166 and carbon-11-NNC 756. J. Nucl. Med. 1994, 35, 1916-20. (Pubitemid 24376603)
17. 76Br-labeled NNC 22-0010, selective dopamine D1 receptor radioligands for PET. Nucl. Med. Biol. 1996, 23, 837-844. (Pubitemid 26342489)
18. 11C]NNC 22-0215, a metabolically stable dopamine D1 radioligand for PET. Nucl. Med. Biol. 1998, 25, 503-508. (Pubitemid 28312333)
19. 76Br]A-69024: a non-benzazepine radioligand for studies of dopamine D1 receptors using PET. Nucl. Med. Biol. 2002, 29, 295-302. (Pubitemid 34258550)
20. 11C]A-69024: a potent and selective nonbenzazepine radiotracer for in vivo studies of dopamine D1 receptors. Nucl. Med. Biol. 1995, 22, 221-6.
21. 11C]A-69024 and positron emission tomography. J. Pharm. Sci. 2008, 97, 2811-2819.
22. Chan, G.L.Y.; Holden, J.E.; Stoessl, A.J.; Doudet, D.J.; Wang, Y.; Dobko, T.; Morrison, K.S.; Huser, J.M.; English, C.; Legg, B.; Schulzer, M.; Calne, D.B.; Ruth, T.J. Reproducibility of the distribution of carbon-11-SCH 23390, a dopamine D1 receptor tracer, in normal subjects. J. Nucl. Med. 1998, 39, 792-797. (Pubitemid 28216725)
23. 11C]raclopride binding in primate brains. Neuropharmacology 1999, 38, 331-338. (Pubitemid 29097716)
24. 11C]SCH23390 binding to the striatal D1 dopamine receptors, but the facilitation enhances phosphodiesterase type-IV activity through D1 receptors: PET studies in the conscious monkey brain. Synapse 2001, 42, 258-265. (Pubitemid 33027299)
25. Reimold, M.; Solbach, C.; Noda, S.; Schaefer, J.E.; Bartels, M.; Beneke, M.; Machulla, H.J.; Bares, R.; Glaser, T.; Wormstall, H. Occupancy of dopamine D1, D2 and serotonin2A receptors in schizophrenic patients treated with flupentixol in comparison with risperidone and haloperidol. Psychopharmacology 2007, 190, 241-249. (Pubitemid 46011184)
26. Jucaite, A.; Forssberg, H.; Karlsson, P.; Halldin, C.; Farde, L. Age-related reduction in dopamine D1 receptors in the human brain: From late childhood to adulthood, a positron emission tomography study. Neuroscience 2010, 167, 104-110.
27. Baeckman, L.; Karlsson, S.; Fischer, H.; Karlsson, P.; Brehmer, Y.; Rieckmann, A.; MacDonald, S.W.S.; Farde, L.; Nyberg, L. Dopamine D1 receptors and age differences in brain activation during working memory. Neurobiol. Aging 2011, 32, 1849-1856.
28. Karlsson, S.; Rieckmann, A.; Karlsson, P.; Farde, L.; Nyberg, L.; Baeckman, L. Relationship of dopamine D1 receptor binding in striatal and extrastriatal regions to cognitive functioning in healthy humans. NeuroImage 2011, 57, 346-351.
29. Manahan-Vaughan, D.; Kulla, A. Regulation of depotentiation and long-term potentiation in the dentate gyrus of freely moving rats by dopamine D2-like receptors. Cereb. Cortex 2003, 13, 123-35. (Pubitemid 36084041)
30. 18F-haloperidol: potential agents for imaging the dopamine receptor. Life Sci. 1983, 33, 1687-93. (Pubitemid 13010011)
31. Wagner, H.N., Jr.; Burns, H.D.; Dannals, R.F.; Wong, D.F.; Langstrom, B.; Duelfer, T.; Frost, J.J.; Ravert, H.T.; Links, J.M.; et al. Imaging dopamine receptors in the human brain by positron tomography. Science 1983, 221, 1264-6. (Pubitemid 13001277)
32. 18F]-N-Methylspiroperidol: the radioligand of choice for PET studies of the dopamine receptor in human brain. Life Sci. 1985, 36, 1359-66. (Pubitemid 15076842)
33. 18F]-fluoroethyl)- spiperone: a novel ligand for cerebral dopamine receptor studies with PET. Life Sci. 1987, 40, 81-8. (Pubitemid 17226128)
34. 18F- labeled spiperone analog for positron emission tomographic studies of the dopamine receptor. Nucl. Med. Biol. 1988, 15, 83-97. (Pubitemid 18013866)
35. 76Br- bromospiroperidol: a new tool for quantitative in-vivo imaging of neuroleptic receptors. Life Sci. 1984, 35, 1349-56. (Pubitemid 14072364)
36. Peroutka, S.J.; Snyder, S.H. Relationship of neuroleptic drug effects at brain dopamine, serotonin, α-adrenergic, and histamine receptors to clinical potency. Am. J. Psychiatry 1980, 137, 1518-22. (Pubitemid 11196805)
37. Leysen, J.E.; Niemegeers, C.J.; Tollenaere, J.P.; Laduron, P.M. Serotonergic component of neuroleptic receptors. Nature 1978, 272, 168-71. (Pubitemid 8280681)
38. Howlett, D.R.; Morris, H.; Nahorski, S.R. Anomalous properties of [3H]spiperone binding sites in various areas of the rat limbic system. Mol. Pharmacol. 1979, 15, 506-14. (Pubitemid 9203067)
39. Farde, L.; Ehrin, E.; Eriksson, L.; Greitz, T.; Hall, H.; Hedstrom, C.G.; Litton, J.E.; Sedvall, G. Substituted benzamides as ligands for visualization of dopamine receptor binding in the human brain by positron emission tomography. Proc. Natl. Acad. Sci. U. S. A. 1985, 82, 3863-7. (Pubitemid 15246452)
40. Halldin, C.; Farde, L.; Hoegberg, T.; Hall, H.; Sedvall, G. Carbon-11 labeling of eticlopride in two different positions - A selective high-affinity ligand for the study of dopamine D-2 receptors using PET. Appl. Radiat. Isot. 1990, 41, 669-74. (Pubitemid 20241062)
41. 18F]fluoropropylepidepride as a potential PET radioligand for imaging dopamine D2 receptors. Synapse 1993, 15, 169-76. (Pubitemid 23339509)
42. 18F]fluoropyrrolidinyl analogs of eticlopride as potential in vivo radioligands for dopamine D2 receptors. Chem. Pharm. Bull. 1992, 40, 1793-8.
43. Sasaki, S.; Takao, F.; Watanabe, K.; Obana, N.; Maeda, M.; Fukumura, T.; Takehara, S. New fluorinated dopamine D2 ligands with benzofuran skeleton. The synthesis and in vitro evaluation. Chem. Pharm. Bull. 1993, 41, 296-300. (Pubitemid 23128191)
44. 18F]fallypride in nonhuman primates. Synapse 2000, 38, 71-9. (Pubitemid 30659620)
45. 18F]MBP in baboon brain. Synapse 1995, 19, 177-87.
46. Mach, R.H.; Nader, M.A.; Ehrenkaufer, R.L.; Line, S.W.; Smith, C.R.; Luedtke, R.R.; Kung, M.P.; Kung, H.F.; Lyons, D.; Morton, T.E. Comparison of two fluorine-18 labeled benzamide derivatives that bind reversibly to dopamine D2 receptors: in vitro binding studies and positron emission tomography. Synapse 1996, 24, 322-33. (Pubitemid 26418684)
47. 18Flabeled ligand. Nucl. Med. Biol. 1995, 22, 809-15.
48. 11C] propylnorapomorphine: a positron-labeled dopamine agonist for PET imaging of D2 receptors. Nucl. Med. Biol. 2000, 27, 533-539.
49. 11C]MNPA in cynomolgus monkey. Nucl. Med. Biol. 2005, 32, 353-360. (Pubitemid 40692685)
50. 11C]MNPA binding to dopamine D2 receptors and response to methamphetamine challenge in monkey brain. Synapse 2009, 63, 534-537.
51. 11C-ZYY-339 in rodents and imaging in non-human primates by PET. Synapse 2004, 54, 83-91. (Pubitemid 39315093)
52. Kessler, R.M.; Ansari, M.S.; Riccardi, P.; Li, R.; Jayathilake, K.; Dawant, B.; Meltzer, H.Y. Occupancy of striatal and extrastriatal dopamine D2/D3 receptors by olanzapine and haloperidol. Neuropsychopharmacology 2005, 30, 2283-9. (Pubitemid 41643981)
53. Mizrahi, R.; Rusjan, P.; Agid, O.; Graff, A.; Mamo, D.C.; Zipursky, R.B.; Kapur, S. Adverse subjective experience with antipsychotics and its relationship to striatal and extrastriatal D2 receptors: a PET study in schizophrenia. Am. J. Psychiatry 2007, 164, 630-7. (Pubitemid 46650195)
54. Agid, O.; Mamo, D.; Ginovart, N.; Vitcu, I.; Wilson, A.A.; Zipursky, R.B.; Kapur, S. Striatal vs extrastriatal dopamine D2 receptors in antipsychotic response- A double-blind PET study in schizophrenia. Neuropsychopharmacology 2007, 32, 1209-15. (Pubitemid 46788848)
55. Nikisch, G.; Baumann, P.; Kiessling, B.; Reinert, M.; Wiedemann, G.; Kehr, J.; Mathe, A.A.; Piel, M.; Roesch, F.; Weisser, H.; Schneider, P.; Hertel, A. Relationship between dopamine D2 receptor occupancy, clinical response, and drug and monoamine metabolites levels in plasma and cerebrospinal fluid. A pilot study in patients suffering from first-episode schizophrenia treated with quetiapine. J. Psychiatr. Res. 2010, 44, 754-9.
56. 11C]raclopride PET. J Psychopharmacol 2011, 25, 1329-36.
57. Mizrahi, R.; Mamo, D.; Rusjan, P.; Graff, A.; Houle, S.; Kapur, S. The relationship between subjective well-being and dopamine D2 receptors in patients treated with a dopamine partial agonist and full antagonist antipsychotics. Int. J. Neuropsychopharmacol. 2009, 12, 715-21.
58. 11C] raclopride PET study. NeuroImage 2006, 33, 907-12. (Pubitemid 44584757)
59. Vilkman, H.; Kajander, J.; Aalto, S.; Vahlberg, T.; Nagren, K.; Allonen, T.; Syvalahti, E.; Hietala, J. The effects of lorazepam on extrastriatal dopamine D(2/3)-receptors-A double-blind randomized placebo-controlled PET study. Psychiatry Res 2009, 174, 130-7.
60. 11C]FLB 457 in healthy subjects. Eur. J. Nucl. Med. Mol. Imaging 2009, 36, 475-83.
61. 11C](R)-2-CH3O-N-n-propylnorapomorphine. Int. J. Neuropsychopharmacol. 2011, 14, 83-9.
62. Levesque, D.; Diaz, J.; Pilon, C.; Martres, M.P.; Giros, B.; Souil, E.; Schott, D.; Morgat, J.L.; Schwartz, J.C.; Sokoloff, P. Identification, characterization, and localization of the dopamine D3 receptor in rat brain using 7-[3H]hydroxy-N, N-di-n-propyl-2-aminotetralin. Proc. Natl. Acad. Sci. U. S. A. 1992, 89, 8155-9.
63. Akunne, H.C.; Towers, P.; Ellis, G.J.; Dijkstra, D.; Wikstrom, H.; Heffner, T.G.; Wise, L.D.; Pugsley, T.A. Characterization of binding of [3H]PD 128907, a selective dopamine D3 receptor agonist ligand, to CHO-K1 cells. Life Sci. 1995, 57, 1401-10.
64. Schotte, A.; Janssen, P.F.M.; Bonaventure, P.; Leysen, J.E. Endogenous dopamine limits the binding of antipsychotic drugs to D3 receptors in the rat brain: A quantitative autoradiographic study. Histochem. J. 1996, 28, 791-799. (Pubitemid 26414169)
65. Tani, Y.; Ishihara, T.; Kanai, T.; Ohno, T.; Andersson, J.; Lilja, A.; Antoni, G.; Fasth, K.J.; Bjurling, P.; et al. Effects of 6R-L-erythro-5, 6, 7, 8-tetrahydrobiopterin on the dopaminergic and cholinergic receptors as evaluated by positron emission tomography in the Rhesus monkey. J. Neural Transm. Gen. Sect. 1995, 102, 189-208. (Pubitemid 26010727)
66. 11C]methoxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl) butylcinnamoylamides. Bioorg. Med. Chem. 2005, 13, 6233-6243. (Pubitemid 41400147)
67. 18F-labeled dopamine D3 receptor ligands as potential PET imaging agents. Bioorg. Med. Chem. Lett. 2005, 15, 4819-23. (Pubitemid 41354813)
68. 11C-Labeling of N-[4-[4-(2, 3-Dichlorophenyl)piperazin-1-yl]butyl]arylcarboxamide Derivatives and Evaluation as Potential Radioligands for PET Imaging of Dopamine D3 Receptors. J. Med. Chem. 2005, 48, 7018-7023. (Pubitemid 41533124)
69. 11C]methoxyphenyl)piperazin-1-yl]butyl]benzo[b]thiophene- 2-c arboxamide - A potential radiotracer for D3 receptor imaging with PET. Nucl. Med. Biol. 2006, 33, 785-95. (Pubitemid 44247732)
70. 18F-Labeled FAUC 346 and BP 897 Derivatives as Subtype-Selective potential PET Radioligands for the Dopamine D3 Receptor. ChemMedChem. 2008, 67, 219.
71. 18F-Labelled Pyridinylphenyl Amides as Subtype-Selective Radioligands for the Dopamine D3 Receptor. ChemMedChem. 2010, 5, 941-948.
72. 11C]-(+)-4-propyl-3, 4, 4a, 5, 6, 10b-hexahydro-2H-naphtho[1, 2-b][1, 4]oxazin-9-ol as a potential radiotracer for in vivo imaging of the dopamine D2 highaffinity state with positron emission tomography. J. Med. Chem. 2005, 48, 4153-60. (Pubitemid 40800622)
73. Rabiner, E.A.; Slifstein, M.; Nobrega, J.; Plisson, C.; Huiban, M.; Raymond, R.; Diwan, M.; Wilson, A.A.; McCormick, P.; Gentile, G.; Gunn, R.N.; Laruelle, M.A. In vivo quantification of regional dopamine-D3 receptor binding potential of (+)-PHNO: studies in non-human primates and transgenic mice. Synapse 2009, 63, 782-793.
74. Bennacef, I.; Salinas, C.A.; Bonasera, T.A.; Gunn, R.N.; Audrain, H.; Jakobsen, S.; Nabulsi, N.; Weinzimmer, D.; Carson, R.E.; Huang, Y.; Holmes, I.; Micheli, F.; Heidbreder, C.; Gentile, G.; Rossi, T.; Laruelle, M. Dopamine D3 receptor antagonists: The quest for a potentially selective PET ligand. Part 3: Radiosynthesis and in vivo studies. Bioorg. Med. Chem. Lett. 2009, 19, 5056-5059.
75. Mach, R.H.; Tu, Z.; Xu, J.; Li, S.; Jones, L.A.; Taylor, M.; Luedtke, R.R.; Derdeyn, C.P.; Perlmutter, J.S.; Mintun, M.A. Endogenous dopamine (DA) competes with the binding of a radiolabeled D3 receptor partial agonist in vivo: A positron emission tomography study. Synapse 2011, 65, 724-732.
76. 11C]-(+)-PHNO: Dissection of D3 signal and anatomy. NeuroImage 2011, 54, 264-277.
77. Ariano, M.A.; Wang, J.; Noblett, K.L.; Larson, E.R.; Sibley, D.R. Cellular distribution of the rat D-4 dopamine receptor protein in the CNS using antireceptor antisera. Brain Res. 1997, 752, 26-34. (Pubitemid 27143894)
78. Primus, R.J.; Thurkauf, A.; Xu, J.; Yevich, E.; McInerney, S.; Shaw, K.; Tallman, J.F.; Gallager, D.W. Localization and characterization of dopamine D4 binding sites in rat and human brain by use of the novel, D4 receptorselective ligand [3H]NGD 94-1. J. Pharmacol. Exp. Therap. 1997, 282, 1020-1027. (Pubitemid 27340208)
79. Khan, Z.U.; Gutierrez, A.; Martin, R.; Penafiel, A.; Rivera, A.; De La Calle, A. Differential regional and cellular distribution of dopamine D2-like receptors: an immunocytochemical study of subtype-specific antibodies in rat and human brain. J. Comp. Neurol. 1998, 402, 353-71. (Pubitemid 28541684)
80. Defagot, M.C.; Antonelli, M.C. Autoradiographic localization of the putative D4 dopamine receptor in rat brain. Neurochem. Res. 1997, 22, 401-7. (Pubitemid 27184704)
81. Noain, D.; Avale, M.E.; Wedemeyer, C.; Calvo, D.; Peper, M.; Rubinstein, M. Identification of brain neurons expressing the dopamine D4 receptor gene using BAC transgenic mice. Eur. J. Neurosci. 2006, 24, 2429-38. (Pubitemid 44726757)
82. Tarazi, F.I.; Kula, N.S.; Baldessarini, R.J. Regional distribution of dopamine D4 receptors in rat forebrain. Neuroreport 1997, 8, 3423-6. (Pubitemid 27497456)
83. Seeman, P.; Guan, H.C.; Van Tol, H.H. Dopamine D4 receptors elevated in schizophrenia. Nature 1993, 365, 441-445. (Pubitemid 23311038)
84. Oak, J.N.; Oldenhof, J.; Van Tol, H.H.M. The dopamine D-4 receptor: one decade of research. Eur. J. Pharmacol. 2000, 405, 303-327.
85. Wong, A.H.C.; Van Tol, H.H.M. The dopamine D-4 receptors and mechanisms of antipsychotic atypicality. Prog. Neu-Psych. Bio. Psych. 2003, 27, 1091-1099. (Pubitemid 37464955)
86. Boy, C.; Klimke, A.; Holschbach, M.; Herzog, H.; Mühlensiepen, H.; Kops, E.R.; Sonnenberg, F.; Gaebel, W.; Stöcklin, G.; Markstein, R.; Müller-Gärtner, H.W. Imaging dopamine D-4 receptors in the living primate brain: A positron emission tomography study using the novel D-1/D-4 antagonist C-11 SDZ GLC 756. Synapse 1998, 30, 341-350. (Pubitemid 28506989)
87. Langer, O.; Halldin, C.; Chou, Y.H.; Sandell, J.; Swahn, C.G.; Nagren, K.; Perrone, R.; Berardi, F.; Leopoldo, M.; Farde, L. Carbon-11 PB-12: An attempt to visualize the dopamine D4 receptor in the primate brain with positron emission tomography. Nucl. Med. Biol. 2000, 27, 707-714. (Pubitemid 32058808)
88. 11C] methoxybenzamide. Nucl. Med. Biol. 2002, 29, 233-241. (Pubitemid 34127957)
89. 11C)-2-naphthalenyl ester (SB-235753), as a putative dopamine D4 receptors antagonist for PET. J. Labelled Compd. Radiopharm. 2000, 43, 359-374. (Pubitemid 30170992)
90. Oh, S.-J.; Lee, K.C.; Lee, S.-Y.; Ryu, E.K.; Saji, H.; Choe, Y.S.; Chi, D.Y.; Kim, S.E.; Lee, J.; Kim, B.-T. Synthesis and evaluation of fluorinesubstituted 1H-pyrrolo[2, 3-b]pyridine derivatives for dopamine D4 receptor imaging. Bioorg. Med. Chem. 2004, 12, 5505-5513. (Pubitemid 39304050)
91. Hübner, H.; Kraxner, J.; Gmeiner, P. Cyanoindole derivatives as highly selective dopamine D4 receptor partial agonists: Solid-phase synthesis, binding assays, and functional experiments. J. Med. Chem. 2000, 43, 4563-4569. (Pubitemid 32046881)
92. Tietze, R.; Hocke, C.; Löber, S.; Hübner, H.; Kuwert, T.; Gmeiner, P.; Prante, O. Syntheses and radiofluorination of two derivatives of 5-cyanoindole as selective ligands for the dopamine subtype-4 receptor. J. Labelled Compd. Radiopharm. 2006, 49, 55-70. (Pubitemid 43242618)
93. Tietze, R.; Löber, S.; Hübner, H.; Gmeiner, P.; Kuwert, T.; Prante, O. Discovery of a dopamine D4 selective PET ligand candidate taking advantage of a click chemistry based REM linker. Bioorg. Med. Chem. Lett. 2008, 18, 983-988. (Pubitemid 351179345)
94. Löber, S.; Hübner, H.; Gmeiner, P. Azaindole derivatives with high affinity for the dopamine D4 receptor: synthesis, ligand binding studies and comparison of molecular electrostatic potential maps. Bioorg. Med. Chem. Lett. 1999, 9, 97-102. (Pubitemid 29023305)
95. Prante, O.; Löber, S.; Hübner, H.; Gmeiner, P.; Kuwert, T. Synthesis and in vitro evaluation of iodine labelled pyrazolo[1, 5-a]pyridines as highly selective dopamine D4 receptor ligands. J. Labelled Compd. Radiopharm. 2001, 44, 849-858. (Pubitemid 33630373)
96. Löber, S.; Hübner, H.; Utz, W.; Gmeiner, P. Rationally based efficacy tuning of selective dopamine D4 receptor ligands leading to the complete antagonist 2-[4-(4-chlorophenyl)piperazin-1-yl]methylpyrazolo[1, 5-a]pyridine (FAUC 213). J. Med. Chem. 2001, 44, 2691-2694. (Pubitemid 32879710)
97. Prante, O.; Hocke, C.; Löber, S.; Hübner, H.; Gmeiner, P.; Kuwert, T. Tissue distribution of radioiodinated FAUC113 -Assessment of a pyrazolo[1, 5-a]pyridine based dopamine D4 receptor radioligand candidate. Nuklearmedizin 2006, 45, 41-48. (Pubitemid 44070820)
98. Prante, O.; Tietze, R.; Hocke, C.; Löber, S.; Hübner, H.; Kuwert, T.; Gmeiner, P. Synthesis, radiofluorination, and in vitro evaluation of pyrazolo[1, 5-a]pyridine-based dopamine D4 receptor ligands: discovery of an inverse agonist radioligand for PET. J. Med. Chem. 2008, 51, 1800-10. (Pubitemid 351438862)
99. 18F-Labeled Benzodioxine Piperazine-Based Dopamine D4 Receptor Ligands: Lipophilicity as a Determinate of Nonspecific Binding. J. Med. Chem. 2011, 54, 8343-8352.
100. Giorgioni, G.; Piergentili, A.; Ruggieri, S.; Quaglia, W. Dopamine D5 receptors: a challenge to medicinal chemists. Mini-Rev. Med. Chem. 2008, 8, 976-995.
101. Elsinga, P.H.; Hatano, K.; Ishiwata, K. PET tracers for imaging of the dopaminergic system. Curr. Med. Chem. 2006, 13, 2139-2153. (Pubitemid 44132606)