PET imaging of norepinephrine transporters

Current Pharmaceutical Design

Volumn 12, Issue 30, 2006, Pages 3831-3845

  Ding, Yu Shin ^a   Lin, Kuo Shyan ^a   Logan, Jean ^a  

^a BROOKHAVEN NATIONAL LABORATORY   (United States)

Author keywords

ADHD; Depression; Methylreboxetine; Nisoxetine; Norepinephrine transporter; PET; Reboxetine; Substance abuse

Indexed keywords

(3 IODOBENZYL)GUANIDINE I 123; 2 HYDROXYDESIPRAMINE; 2 IODONISOXETINE I 125; 4 IODOTOMOXETINE C 11; AMPHETAMINE; ANTIDEPRESSANT AGENT; ATOMOXETINE; BRAIN MONOAMINE; CARBON 11; DESIPRAMINE; DESIPRAMINE C 11; DOPAMINE TRANSPORTER; FLUORODEOXYGLUCOSE F 18; LORTALAMINE; LORTALAMINE C 11; MAZINDOL; METHYLPHENIDATE; METHYLREBOXETINE C 11; NISOXETINE; NISOXETINE C 11; NORADRENALIN TRANSPORTER; OXAPROTILINE; OXAPROTILINE C 11; RADIOLIGAND; REBOXETINE; SEROTONIN TRANSPORTER; TALOPRAM C 11; TALSUPRAM; TALSUPRAM C 11; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ALZHEIMER DISEASE; ATTENTION DEFICIT DISORDER; AUTOPSY; CENTRAL NERVOUS SYSTEM DISEASE; CORPUS STRIATUM; DEGENERATIVE DISEASE; DEPRESSION; DRUG BINDING SITE; DRUG DEPENDENCE; DRUG DESIGN; DRUG PROTEIN BINDING; ENANTIOMER; HUMAN; IMAGING SYSTEM; IN VITRO STUDY; IN VIVO STUDY; ISOTOPE LABELING; MENTAL DISEASE; NEUROIMAGING; NEUROLOGIC DISEASE; NONHUMAN; PARKINSON DISEASE; PATHOPHYSIOLOGY; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; REVIEW; THALAMUS; UNSPECIFIED SIDE EFFECT;

ANIMALS; HUMANS; NOREPINEPHRINE PLASMA MEMBRANE TRANSPORT PROTEINS; POSITRON-EMISSION TOMOGRAPHY; RADIOPHARMACEUTICALS;

EID: 33749824386     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161206778559687     Document Type: Review

References (118)

1. Glowinski J, Axelrod J. Inhibition of uptake of tritiated-noradrenaline in the intact rat brain by imipramine and structurally related compounds. Nature 1964; 204: 1318-1319.
2. 3H-NE in isolated vasa deferentia and atria of the rat. Naunyn-Schmiedebergs Arch Pharmacol 1989; 340: 502-508.
3. Paczkowski NJ, Vuocolo BE, Bryan-Lluka LJ. Conclusive evidence for distinct transporters for 5-hydroxyhyptamine and noradrenaline in pulmonary endothelial cells of the rat. Naunyn-Schmiedebergs Arch Pharmacol 1996; 353: 423-430.
4. Zahniser NR, Doolen S. Chronic and acute regulation of Na(+)/Cl (-)-dependent neurotransmitter transporters: drugs, substrates, presynaptic receptors, and signaling systems. Pharmacol Ther 2001; 92: 21-55.
5. Foote SL, Bloom FE, Aston-Jones G. Nucleus locus ceruleus: new evidence of anatomical and physiological specificity. Physiol Rev 1983; 63: 844-914.
6. Saper CB. Fun of the locus coeruleus. Trends Neurosci 1987; 10: 343-344.
7. Charney DS, Heninger GR, Sternberg DE, Roth RH. Plasma MHPG in depression: effects of acute and chronic desipramine treatment. Psychiatry Res 1981; 5: 217-29.
8. Ordway GA. Pathophysiology of the locus coeruleus in suicide. Ann NY Acad Sci 1997; 836: 233-252.
9. Böhm M, Castellano M, Flesch M, Maack C, Moll M, Paul M, et al. Chamber-specific alterations of norepinephrine uptake sites in cardiac hypertrophy. Hypertension 1998; 32: 831-837.
10. Ungerer M, Chlistalla A, Richardt G. Upregulation of cardiac uptake 1 carrier in ischemic and nonischemic rat heart. Circ Res 1996; 78: 1037-1043.
11. Tejani-Butt SM, Yang J, Zaffar H. Norepinephrine transporter sites are decreased in the locus coeruleus in Alzheimer's disease. Brain Res 1993; 631: 147-150.
12. Jellinger KA. Morphological substrates of dementia in parkinsonism: a critical update. J Neural Transm 1997; [Suppl] 51: 57-82.
13. Owens MJ, Morgan WN, Plott SJ, Nemeroff CB. Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites. J Pharmacol Exp Ther 1997; 283: 1305-1322.
14. Burrows GD, Maguire KP, Norman TR. Antidepressant efficacy and tolerability of the selective norepinephrine reuptake inhibitor reboxetine: a review. J Clin Psychiatry 59(Suppl 14): 4-7.
15. Sacchetti G, Bernini M, Bianchetti A, Parini S, Invernizzi RW, Samanin R. Studies on the acute and chronic effects of reboxetine on extracellular noradrenaline and other monoamines in the rat brain. Br J Pharmacol 1999; 128: 1332-1338.
16. Ritz MC, Cone EJ, Kuhar MJ. Cocaine inhibition of ligand binding at dopamine, norepinephrine and serotonin transporters: a structure-activity study. Life Sci 1990; 46: 635-645.
17. Wall SC, Gu H, Rudnick G. Biogenic amine flux mediated by cloned transporters stably expressed in cultured cell lines: amphetamine specificity for inhibition and efflux. Mol Pharmacol 1995; 47: 544-550.
18. 3H]desipramin. Proc Natl Acad Sci USA 1981; 78: 5250-4.
19. 3H]desipramine binding associated with neuronal norepinephrine uptake sites in rat brain membranes. J Neurosci 1982; 2: 1515-25.
20. Lee CM, Javitch JA, Snyder SH. Recognition sites for norepinephrine uptake: regulation by neurotransmitter. Science 1983; 220: 626-629.
21. 3H-desmethylimipramine binding sites in rat brain. Eur J Pharmacol 1982; 82: 245-246.
22. 3H]nisoxetine: a radioligand for quantitation of norepinephrine uptake sites by autoradiography or by homogenate binding. J Pharmacol Exp Ther 1992; 260: 427-36.
23. 3H]nisoxetine binding sites in the cat brain: an autoradiographic study. Neuroscience 1995; 69: 259-270.
24. Fowler JS, MacGregor RR, Ansari AN, Atkins HL, Wolf AP. Radiopharmaceuticals. 12. A new rapid synthesis of carbon-11 labeled norepinephrine hydrochloride. J Med Chem 1974; 17: 246-248.
25. Farde L, Halldin C, Nagren Y, Suhara T, Karlsson P, Schoeps KO, et al. Positron emission tomography shows high specific uptake of racemic carbon-11 labelled norepinephrine in the primate heart. Eur J Nucl Med 1994; 21: 345-7.
26. 18F]fluoronorepinephrine via the nucleophilic aromatic substitution reaction. J Med Chem 1991a; 34: 767-771.
27. 18F]fluorodopamine for PET studies of sympathetic nervous tissue. J Med Chem 1991b; 34: 861-863.
28. 18F]fluoronorepinephrine in baboon; heart uptake, metabolism and the effect of desipramine. J Nucl Med 1993a; 34: 619.
29. 4) for mechanistic studies with positron emission tomography. J Label Comp Radiopharm 1993b; 33: 645-654.
30. 18F]fluorodopamine in living baboon heart: Selective imaging and control of radiotracer metabolism using the deuterium isotope effect. J Neurochem 1995; 65: 682-690.
31. 131I] meta-iodobenzylguanidine: concise communication. J Nucl Med 1981; 22: 358-64.
32. 18F] fluorometaraminol. J Med Chem 1990; 33(3): 956-64.
33. 11C]phenylephrine kinetics: studies in isolated rat heart. J Nucl Med 1999; 40: 323-330.
34. Munch G, Nguyen NT, Nekolla S, Ziegler S, Muzik O, Chakraborty P, et al. Evaluation of sympathetic nerve terminals with [(11)Clepinephrine and [(11)C]hydroxyephedrine and positron emission tomography. Circulation 2000;101(5): 516-23.
35. 3H]mazindol autoradiography. J Neurosci 1985; 5: 1513-21.
36. 11C]nisoxetine, a norepinephrine uptake inhibitor. Nucl Med Biol 1989; 16: 771-774.
37. Chumpradit S, Kung MP, Panyachotipunm V, Prapansiri C, Foulon BP, Brooks SA, et al. Iodinated tomoxetine derivatives as selective ligands for serotonin and norepinephrine uptake sites. J Med Chem 1992; 35: 4492-4497.
38. Wilson AA, Johnson DP, Mozley D, Hussey D, Ginovart N, Nobrega J, et al. Synthesis and in vivo evaluation of novel radiotracers for the in vivo imaging of the norepinephrine transporter. Nucl Med Biol 2003; 30: 85-92.
39. 11C]MeNER. Nucl Med Biol 2003; 30: 707-14.
40. Ding YS, Lin KS, Garza V, Carter P, Alexoff D, Logan J, et al. Evaluation of a new norepinephrine transporter PET ligand in baboons, both in brain and peripheral organs. Synapse 2003; 50: 345-352.
41. Post RM. Central norepinephrine metabolism in affective illness: MHPG in CSF. Science 1973; 179: 1002-1003.
42. Greenberg PE, Stiglin LE, Finkelstein SN, Berndt ER. Depression: a neglected major illness. J Clin Psychiatry 1993; 54: 419-424.
43. Hays RD, Wells KB, Sherbourne CD, Rogers W, Spritzer K. Functioning and well-being outcomes of patients with depression compared with chronic general medical illnesses. Arch Gen Psychiatry 1995; 52: 11-19.
44. Mulrow CD, Williams JW Jr, Chiquette E, Aguilar C, Hitchcock-Noel P, Lee S, et al. Efficacy of newer medications for treating depression in primary care patients. Am J Med 2000; 108: 54-64.
45. Tatsumi M, Groshan K, Blakely RD, Richelson E. Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol 1997; 340: 249-58.
46. Klimek V, Stockmeier C, Overholser J, Meltzer HY, Kalka S, Dilley G, et al. Reduced levels of norepinephrine transporters in the locus coeruleus in major depression. J Neurosci 1997; 17: 8451-8458.
47. Montgomery SA. Is there a role for a pure noradrenergic drug in the treatment of depression? Eur Neuropsychopharm 1997; 7 (Suppl. 1): S3-S9.
48. Van Dongen PM. The human locus coeruleus in neurology and psychiatry. (Parkinson's, Lewy body, Hallervorden-Spatz, Alzheimer's and Korsakoffs disease, (pre)senile dementia, schizophrenia, affective disorders, psychosis). Prog Neurobiol 1981; 17: 97-139.
49. Carlsson A. The impact of catecholamine research on medical science and practice. In: Usdin E, Kopin IJ, Barchas J Eds, Catecholamines: basic and clinic frontiers. Pergamon Press, New York 1979; 4-19
50. Ohama E, Ikuta F. Parkinson's disease: Distribution of Lewy bodies and monoamine neuron systems. Acta Neuropath 1976; 34: 311-319.
51. Barkley R. ADHD and the nature of self-control. Guilford, New York 1997.
52. West WB, van Groll BJ, Appel JB. Stimulus effects of damphetamine II: DA, NE and 5-HT mechanisms. Pharmacol Biochem Behav 1995; 51: 69-76.
53. Pliszka SR, McCracken JF, Maas JW. Catecholamines in attention-deficit hyperactivity disorder: current perspectives. J Am Acad Child Adolesc Psychiatry 1996; 35: 264-272.
54. 11C]d-threo and 1-threo-methylphenidate in the human and baboon brain. Psychopharmacology 1997; 131: 71-78.
55. Solanto MV. Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration. Behav Brain Res 1998; 94: 127-152.
56. Volkow ND, Wang GJ, Fowler JS, Gatley SJ, Logan J, Ding YS, et al. Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. Am J Psychiatry 1998; 155: 1325-1331.
57. Fleckenstein AE, Gibb JW, Hanson GR. Differential effects of stimulants on monoaminergic transporters: pharmacological consequences and implications for neurotoxicity. Eur J Pharmacol 2000; 406: 1-13.
58. Eshleman AJ, Carmolli M, Cumbay M, Martens CR, Neve KA, Janowsky A. Characteristics of drug interactions with recombinant biogenic amine transporters expressed in the same cell type. J Pharmacol Exp Ther 1999; 289: 877-885.
59. Biederman J, Spencer T. Depressive disorders in childhood and adolescence: a clinical perspective. J Child Adolesc Psychopharmacol 1999; 9: 233-237.
60. Volkow ND, Wang GJ, Fowler JS, Gatley SJ, Logan J, Ding YS, et al. Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. Am J Psychiatry 1998; 155: 1325-1331.
61. Volkow ND, Wang GJ, Fowler JS, Gatley SJ, Logan J, Ding Y-S, et al. Blockade of striatal dopamine transporters by intravenous methylphenidate is not sufficient to induce self reports of "High". J Pharmacol Exp Ther 1999; 288: 14-20.
62. Volkow ND, Fowler JS, Wang GJ, Ding YS, Gatley SJ. Role of dopamine in the therapeutic and reinforcing effects of methylphenidate in humans: results from imaging studies. Eur Neuropsychopharmacol 2002a; 12: 557-66.
63. Volkow ND, Wang G-J, Fowler JS, Logan J, Franceschi D, Maynard L, et al. Relationship between blockade of dopamine transporters by oral methylphenidate and the increases in extracellular dopamine: therapeutic implications. Synapse 2002b; 43: 181-87.
64. Volkow ND, Fowler JS, Wang GJ. Role of dopamine in drug reinforcement and addiction in humans: results from imaging studies. Behav Pharmacol 2002c; 13: 355-66.
65. Amara SG, Sonders MS. Neurotransmitter transporters as molecular targets for addictive drugs. Drug Alcohol Depend 1998; 51: 87-96.
66. Roberts DC, Koob GF, Klonoff P, Fibiger HC. Extinction and recovery of cocaine self-administration following 6-hydroxydopamine lesions of the nucleus accumbens. Pharmacol Biochem Behav 1980; 12: 781-787.
67. Ritz MC, Lamb RJ, Goldberg SR, Kuhar MJ. Cocaine receptors on dopamine transporters are related to self-administration of cocaine. Science 1987; 237: 1219-1223.
68. Giros B, Jaber M, Jones SR, Wightman RM, Caron MG. Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature 1996; 379: 606-612.
69. Letchworth SR, Nader MA, Smith HR, Friedman DP, Porrino LJ. Progression of changes in dopamine transporter binding site density as a result of cocaine self-administration in rhesus monkeys. J Neurosci 2001; 21: 2799-2807.
70. Nader MA, Daunais JB, Moore T, Nader SH, Moore RJ, Smith HR, et al. Effects of cocaine self-administration on striatal dopamine systems in rhesus monkeys: initial and chronic exposure. Neuropsychopharmacology 2002; 27: 35-46.
71. Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, et al. Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse 2001; 39: 32-41.
72. Madras BK, Kaufman MJ. Cocaine accumulates in dopamine-rich regions of primate brain after i.v. administration: comparison with mazindol distribution. Synapse 1994; 18: 261-275.
73. Burchett SA, Bannon MJ. Serotonin, dopamine and norepinephrine transporter mRNAs: heterogeneity of distribution and response to 'binge' cocaine administration. Brain Res Mol Brain Res 1997; 49: 95-102.
74. Macey DJ, Smith HR, Nader MA, Porrino LJ. Chronic cocaine self-administration upregulates the norepinephrine transporter and alters functional activity in the bed nucleus of the stria terminalis of the rhesus monkey. J Neurosci 2003; 23: 12-6.
75. Beveridge T, Smith HR, Nader MA, Porrino LJ. Effects of chronic cocaine self-administration on norepinephrine transporters in the nonhuman primate brain. Psychopharmacology 2005.
76. Spealman RD. Noradrenergic involvement in the discriminative stimulus effects of cocaine in squirrel monkeys. J Pharmacol Exp Ther 1995; 275: 53-62.
77. Sinden JD, Atrens D. Dopaminergic and noradrenergic inhibition of hypothalamic self-stimulation: differentiation of reward and performance effects. Eur J Pharmacol 1982; 86(2): 237-46.
78. Xu F, Gainetdinov RR, Wetsel WC, Jones SR, Bohn LM, Miller GW, et al. Mice lacking the norepinephrine transporter are supersensitive to psychostimulants. Nat Neurosci 2000; 3: 465-471.
79. Ramamoorthy JD, Ramamoorthy S, Leibach FH, Ganapathy. Human placental monoamine transporters as targets for amphetamines. Am J Obstet Gynecol 1995; 173: 1782-7.
80. Dishino DD, Welch MJ, Kilbourn MR, Raichle ME. Relationship between lipophilicity and brain extraction of C-11-labeled radio-pharmaceuticals. J Nucl Med 1983; 24: 1030-8.
81. 11C]AFM. J Cereb Blood Flow Metab 2002; 22: 1377-1398.
82. 11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents. J Med Chem 2003; 46: 2740-2754.
83. Waterhouse RN. Determination of lipophilicity and its use as a predictor of blood-brain barrier penetration of molecular imaging agents. Mol Imaging Biol 2003; 5: 376-89.
84. Laruelle M, Slifstein M, Huang Y. Relationships between radiotracer properties and image quality in molecular imaging of the brain with positron emission tomography. Mol Imaging Biol 2003; 5: 363-75.
85. Wong DF, Pomper MG. Predicting the success of a radiopharmaceutical for in vivo imaging of central nervous system neuroreceptor systems. Mol Imaging Biol 2003; 5: 350-62.
86. Logan J, Ding Y-S, Lin K-S, Pareto D, Fowler J, Biegon A. Modeling and analysis of PET studies with norepinephrine transporter (NET) ligands: the search for a reference region. Nucl Med Biol 2005; 32: 531-42.
87. Javaid JI, Perel JM, Davis JM. Inhibition of biogenic amines uptake by imipramine, desipramine, 2-OH-imipramine and 2-OH-desipramme in rat brain. Life Sci 1979; 24: 21-28.
88. 3[H]desipramine binding in the peripheral and central nervous system: A specific site associated with the neuronal uptake of noradrenaline. Eur J Pharmacol 1982; 78: 345-351.
89. 11C-labeled desipramine and its metabolite 2-hydroxydesipramine: potential radiotracers for PET studies of the norepinephrine transporter. Nucl Med Biol 1997; 24: 707-711.
90. 11C]talsupram: candidate PET ligands for the norepinephrine transporter. Nucl Med Biol 2004; 31: 705-718.
91. 11C]nisoxetine, a norepinephrine uptake inhibitor. Nucl Med Biol 1989;16: 771-774.
92. Gehlert DR, Hemrick-Luecke SK, Schober DA, Krushinski J, Howbert JJ, Robertson DW, et al. (R)-thionisoxetine, a potent and selective inhibitor of central and peripheral norepinephrine uptake. Life Sci 1995; 56: 1915-20.
93. Ding Y-S, Lin KS, Logan J, Benveniste H, Carter P. Comparative evaluation of PET radiotracers for imaging the norepinephrine transporter: (S, S) and (R, R) enantiomers of reboxetine analogues. J Neurochem 2005; in press.
94. Lin K-S, Ding Y-S. Synthesis, enantiomeric resolution and selective C-11 methylation of a highly selective radioligand for imaging the norepinephrine transporter with positron emission tomography. Chirality 2004; 16: 475-481.
95. Wong EHF, Souders MS, Amara SG, Tinholt PM, Piercey MFP, Hoffmann WP, et al. Reboxetine: A pharmacologically potent, selective, and specific norepinephrine reuptake inhibitor. Biol Psychiat 2000; 47: 818-829.
96. Schou M, Halldin C, Sovago J, Pike VW, Hall H, Gulyas B, et al. PET evaluation of novel radiofluorinated reboxetine analogs as norepinephrine transporter probes in the monkey brain. Synapse 2004; 53: 57-67.
97. 18F]fluoroethyl-5-methoxybenzyl)acetamide, for PET imaging of peripheral benzodiazepine receptor in primate brain. J Med Chem 2004; 47: 2228-2235.
98. 18F]AFM. J Nucl Med 2003; 44: 293P.
99. Lin K-S, Kim S, Ding Y-S. Synthesis, enantiomeric resolution, F-18 labeling and biodistribution of reboxetine analogs: promising radioligands for imaging the norepinephrine transporter with PET. Nucl Med Biol 2005; in press.
100. Raffel DM, Gildersleeve DL, Van Dort ME, Jung YW. 11C-Oxaprotiline: synthesis and initial evaluation as a selective marker of norepinephrine transporters in brain. J Nucl Med 2002; 43: 360P.
101. Chumpradit S, Kung MP, Panyachotipunm V, Prapansiri C, Foulon BP, Brooks SA, et al. Iodinated tomoxetine derivatives as selective ligands for serotonin and norepinephrine uptake sites. J Med Chem 1992; 35: 4492-4497.
102. 11C]DASB. Eur J Nucl Med 2000; 27: 1719-22.
103. Kiyono Y, Kanegawa N, Kawashima H, Kitamura Y, Iida Y, Saji H. Evaluation of radioiodinated (R)-N-methyl-3-(2-iodophenoxy)-3-phenylpropanamine as a ligand for brain norepinephrine transporter imaging. Nucl Med Biol 2004; 31: 147-53.
104. Kung MP, Choi SR, Hou C, Zhuang ZP, Foulon C, Kung HF. Selective binding of 2-[(125)1]iodo-nisoxetine to norepinephrine transporters in the brain. Nucl Med Biol 2004; 31: 533-41.
105. 3H-chlorpromazine to areas in the rat brain. Eur J Pharmacol 1978; 51: 121-127.
106. Ding YS, Lin KS, Logan J, Fowler JS, Volkow ND. Occupancy of brain norepinephrine transporters by cocaine and methylphenidate. J Nucl Med 2004; 45(Suppl): p. 69.
107. Dolle F, Dolci L, Valette H, Hinnen F, Vaufrey F, Guenther I, et al. Synthesis and nicotinic acetylcholine receptor in vivo binding properties of 2-fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine: A new positron emission tomography ligand for nicotinic receptors. J Med Chem 1999; 42: 2251-2259.
108. Avdeef A. Physicochemical profiling (solubility, permeability and charge state). Curr Top Med Chem 2001; 1: 277-351.
109. Avdeef A, Testa B. Physicochemical profiling in drug research: a brief survey of the state-of-the-art of experimental techniques. Cell Mol Life Sci 2002; 59: 1681-1689.
110. van de Waterbeemd H, Smith DA, Jones BC. Lipophilicity in PK design: methyl, ethyl, futile. J Comput Aided Mol Des 2001; 15: 273-286.
111. Kung MP, Essman WD, Frederick D, Meegalla S, Goodman M, Mu M, et al. IPT: a novel iodinated ligand for the CNS dopamine transporter. Synapse 1995, 20:316-24.
112. Fowler JS. Radiotracer chemistry in 2003: better prediction needed. J Nucl Med 2004; 45: 26N-33N.
113. Melloni P, Camiel G, Della Torre A, Bonsignori A, Buonamici M, Pozzi O, et al. Potential antidepressant agents. a-Aryloxy-benzyl derivatives of ethanolamine and morpholine. Eur J Med Chem 1984; 19: 235-242.
114. Bogeso KP, Christensen AV, Hyttel J, Liljefors T. 3-Phenyl-lindanamines. Potential antidepressant activity and potent inhibition of dopamine, norepinephrine, and serotonin uptake. J Med Chem 1985; 28: 1817-28.
115. Depin JC, Betbeder-Matibet A, Bonhomme Y, Muller AJ, Berthelon J-J. Pharmacology of lortalamine, a new potent non-tricyclic antidepressant. Arzneimittel Forschung 1985; 35: 1655-62.
116. Bymaster FP, Lee TC, Knadler MP, Detke MJ, Iyengar S. The dual transporter inhibitor duloxetine: a review of its preclinical pharmacology, pharmacokinetic profile, and clinical results in depression. Curr Pharm Des 2005; 11(12): 1475-93.
117. Guilloteau D, Chalon S. PET and SPECT exploration of central monoaminergic transporters for the development of new drugs and treatments in brain disorders. Curr Pharm Des 2005; 11(25): 3237-45.
118. Tsuang J, Fong TW. Treatment of patients with schizophrenia and substance abuse disorders. Curr Pharm Des 2004; 10(18): 2249-61.