Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

The Ligands of Translocator Protein: Design and Biological Properties

Author(s): Grigory V. Mokrov, Olga A. Deeva and Tatiana A. Gudasheva*

Volume 27, Issue 2, 2021

Published on: 03 September, 2020

Page: [217 - 237] Pages: 21

DOI: 10.2174/1381612826666200903122025

Price: $65

Open Access Journals Promotions 2
Abstract

In 2020, it is already 43 years since Braestrup and Squires discovered 18 kDa translocator protein (TSPO), known until 2006 as "peripheral benzodiazepine receptor". During this time, the functions of this receptor, which is located on the outer membrane of mitochondria, were studied in detail. One of the key functions of TSPO is the transfer of cholesterol from the outer to the inner mitochondrial membrane, which is the limiting stage in the synthesis of neurosteroids. TSPO is also involved in the transport of porphyrins, mitochondrial respiration, the opening of mitochondrial pores, apoptosis and cell proliferation. This review presents current information on the structure of TSPO, the mechanism of its participation in neurosteroidogenesis, as well as endogenous and synthetic TSPO ligands. Particular emphasis is placed on the analysis of approaches to the design of synthetic ligands and their neuropsychotropic activity in vitro and in vivo. The presented review demonstrates the promise of constructing new neuropsychotropic drugs in the series of TSPO ligands.

Keywords: 18 kDa translocator protein TSPO, TSPO ligands, neuropsychotropic activity, drug design, neurosteroids, cholesterol.

« Previous Next »
[1]
Papadopoulos V, Baraldi M, Guilarte TR, et al. Translocator protein (18kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. Trends Pharmacol Sci 2006; 27(8): 402-9.
[http://dx.doi.org/10.1016/j.tips.2006.06.005] [PMID: 16822554]
[2]
Jaremko L, Jaremko M, Giller K, Becker S, Zweckstetter M. Structure of the mitochondrial translocator protein in complex with a diagnostic ligand. Science 2014; 343(6177): 1363-6.
[http://dx.doi.org/10.1126/science.1248725] [PMID: 24653034]
[3]
Li F, Liu J, Liu N, Kuhn LA, Garavito RM, Ferguson-Miller SM. Translocator protein 18 kDa (TSPO): an old protein with new functions? Biochemistry 2016; 55(20): 2821-31.
[4]
Jaremko L, Jaremko M, Giller K, Becker S, Zweckstetter M. Conformational flexibility in the transmembrane protein TSPO chemistry. Chem Eur J 2015; 21(46): 16555-63.
[http://dx.doi.org/10.1002/chem.201502314]
[5]
Guo YZ, Kalathur RC, Liu Q, et al. Structure and activity of tryptophan-rich TSPO proteins. Science 2015; 347(6221): 551-5.
[http://dx.doi.org/10.1126/science.aaa1534]
[6]
Li F, Liu J, Zheng Y, Garavito RM, Ferguson-Miller S. Crystal structures of translocator protein (TSPO) and mutant mimic of a human polymorphism. Science 2015; 347(6221): 555-8.
[7]
Korkhov VM, Sachse C, Short JM, Tate CG. Three-Dimensional Structure of TspO by Electron Cryomicroscopy of Helical Crystals. Structure 2010; 18(6): 677-87.
[http://dx.doi.org/10.1016/j.str.2010.03.001]
[8]
Li H, Papadopoulos V. Peripheral-type benzodiazepine receptor function in cholesterol transport. Identification of a putative cholesterol recognition/interaction amino acid sequence and consensus pattern. Endocrinology 1998; 139(12): 4991-7.
[http://dx.doi.org/10.1210/endo.139.12.6390] [PMID: 9832438]
[9]
Owen DR, Gunn RN, Rabiner EA, et al. Mixed-affinity binding in humans with 18-kDa translocator protein ligands. J Nucl Med 2011; 52(1): 24-32.
[http://dx.doi.org/10.2967/jnumed.110.079459] [PMID: 21149489]
[10]
Owen DR, Lewis AJ, Reynolds R, et al. Variation in binding affinity of the novel anxiolytic XBD173 for the 18 kDa translocator protein in human brain. Synapse 2011; 65(3): 257-9.
[http://dx.doi.org/10.1002/syn.20884] [PMID: 21132812]
[11]
Owen DR, Yeo AJ, Gunn RN, et al. An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. J Cereb Blood Flow Metab 2012; 32(1): 1-5.
[http://dx.doi.org/10.1038/jcbfm.2011.147] [PMID: 22008728]
[12]
Lacapère J-J, Papadopoulos V. Peripheral-type benzodiazepine receptor: structure and function of a cholesterol-binding protein in steroid and bile acid biosynthesis. Steroids 2003; 68(7-8): 569-85.
[http://dx.doi.org/10.1016/S0039-128X(03)00101-6] [PMID: 12957662]
[13]
Casellas P, Galiegue S, Basile AS. Peripheral benzodiazepine receptors and mitochondrial function. Neurochem Int 2002; 40(6): 475-86.
[http://dx.doi.org/10.1016/S0197-0186(01)00118-8] [PMID: 11850104]
[14]
Gavish M, Bachman I, Shoukrun R, et al. Enigma of the peripheral benzodiazepine receptor. Pharmacol Rev 1999; 51(4): 629-50.
[PMID: 10581326]
[15]
Anholt RR, Murphy KM, Mack GE, Snyder SH. Peripheral-type benzodiazepine receptors in the central nervous system: localization to olfactory nerves. J Neurosci 1984; 4(2): 593-603.
[http://dx.doi.org/10.1523/JNEUROSCI.04-02-00593.1984] [PMID: 6321699]
[16]
Bolger GT, Mezey E, Cott J, Weissman BA, Paul SM, Skolnick P. Differential regulation of ‘central’ and ‘peripheral’ benzodiazepine binding sites in the rat olfactory bulb. Eur J Pharmacol 1984; 105(1-2): 143-8.
[http://dx.doi.org/10.1016/0014-2999(84)90658-7] [PMID: 6092112]
[17]
Jayakumar AR, Panickar KS, Norenberg MD. Effects on free radical generation by ligands of the peripheral benzodiazepine receptor in cultured neural cells. J Neurochem 2002; 83(5): 1226-34.
[http://dx.doi.org/10.1046/j.1471-4159.2002.01261.x] [PMID: 12437594]
[18]
Karchewski LA, Bloechlinger S, Woolf CJ. Axonal injury-dependent induction of the peripheral benzodiazepine receptor in small-diameter adult rat primary sensory neurons. Eur J Neurosci 2004; 20(3): 671-83.
[http://dx.doi.org/10.1111/j.1460-9568.2004.03530.x] [PMID: 15255978]
[19]
Papadopoulos V, Amri H, Boujrad N, et al. Peripheral benzodiazepine receptor in cholesterol transport and steroidogenesis. Steroids 1997; 62(1): 21-8.
[http://dx.doi.org/10.1016/S0039-128X(96)00154-7] [PMID: 9029710]
[20]
Hirsch JD, Beyer CF, Malkowitz L, Beer B, Blume AJ. Mitochondrial benzodiazepine receptors mediate inhibition of mitochondrial respiratory control. Mol Pharmacol 1989; 35(1): 157-63.
[PMID: 2464128]
[21]
Corsi L, Geminiani E, Baraldi M. Peripheral benzodiazepine receptor (PBR) new insight in cell proliferation and cell differentiation review. Curr Clin Pharmacol 2008; 3(1): 38-45.
[http://dx.doi.org/10.2174/157488408783329878] [PMID: 18690876]
[22]
Veenman L, Papadopoulos V, Gavish M. Channel-like functions of the 18-kDa translocator protein (TSPO): regulation of apoptosis and steroidogenesis as part of the host-defense response. Curr Pharm Des 2007; 13(23): 2385-405.
[http://dx.doi.org/10.2174/138161207781368710] [PMID: 17692008]
[23]
Papadopoulos V, Liu J, Culty M. Is there a mitochondrial signaling complex facilitating cholesterol import? Mol Cell Endocrinol 2007; 265-6: 59-64.
[http://dx.doi.org/10.1016/j.mce.2006.12.004] [PMID: 17280776]
[24]
Jamin N, Neumann JM, Ostuni MA, et al. Characterization of the cholesterol recognition amino acid consensus sequence of the peripheral-type benzodiazepine receptor. Mol Endocrinol 2005; 19(3): 588-94.
[http://dx.doi.org/10.1210/me.2004-0308] [PMID: 15528269]
[25]
Murail S, Robert JC, Coïc YM, et al. Secondary and tertiary structures of the transmembrane domains of the translocator protein TSPO determined by NMR. Stabilization of the TSPO tertiary fold upon ligand binding. Biochim Biophys Acta 2008; 1778(6): 1375-81.
[http://dx.doi.org/10.1016/j.bbamem.2008.03.012] [PMID: 18420025]
[26]
Papadopoulos V, Aghazadeh Y, Fan J, Campioli E, Zirkin B, Midzak A. Translocator protein-mediated pharmacology of cholesterol transport and steroidogenesis. Mol Cell Endocrinol 2015; 408: 90-8.
[http://dx.doi.org/10.1016/j.mce.2015.03.014] [PMID: 25818881]
[27]
Rone MB, Midzak AS, Issop L, et al. Identification of a dynamic mitochondrial protein complex driving cholesterol import, trafficking, and metabolism to steroid hormones. Mol Endocrinol 2012; 26(11): 1868-82.
[http://dx.doi.org/10.1210/me.2012-1159] [PMID: 22973050]
[28]
Rupprecht R, Papadopoulos V, Rammes G, et al. Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders. Nat Rev Drug Discov 2010; 9(12): 971-88.
[http://dx.doi.org/10.1038/nrd3295] [PMID: 21119734]
[29]
Bordet T, Buisson B, Michaud M, et al. Identification and characterization of cholest-4-en-3-one, oxime (TRO19622), a novel drug candidate for amyotrophic lateral sclerosis. J Pharmacol Exp Ther 2007; 322(2): 709-20.
[http://dx.doi.org/10.1124/jpet.107.123000] [PMID: 17496168]
[30]
Snyder SH, Verma A, Trifiletti RR. The peripheral-type benzodiazepine receptor: a protein of mitochondrial outer membranes utilizing porphyrins as endogenous ligands. FASEB J 1987; 1(4): 282-8.
[http://dx.doi.org/10.1096/fasebj.1.4.2820823] [PMID: 2820823]
[31]
Verma A, Nye JS, Snyder SH. Porphyrins are endogenous ligands for the mitochondrial (peripheral-type) benzodiazepine receptor. Proc Natl Acad Sci USA 1987; 84(8): 2256-60.
[http://dx.doi.org/10.1073/pnas.84.8.2256] [PMID: 3031675]
[32]
Verma A, Snyder SH. Peripheral type benzodiazepine receptors. Annu Rev Pharmacol Toxicol 1989; 29: 307-22.
[http://dx.doi.org/10.1146/annurev.pa.29.040189.001515] [PMID: 2543271]
[33]
Guidotti A, Forchetti CM, Corda MG, Konkel D, Bennett CD, Costa E. Isolation, characterization, and purification to homogeneity of an endogenous polypeptide with agonistic action on benzodiazepine receptors. Proc Natl Acad Sci USA 1983; 80(11): 3531-5.
[http://dx.doi.org/10.1073/pnas.80.11.3531] [PMID: 6304714]
[34]
Bovolin P, Schlichting J, Miyata M, Ferrarese C, Guidotti A, Alho H. Distribution and characterization of diazepam binding inhibitor (DBI) in peripheral tissues of rat. Regul Pept 1990; 29(2-3): 267-81.
[http://dx.doi.org/10.1016/0167-0115(90)90089-F] [PMID: 2171047]
[35]
Ferrero P, Santi MR, Conti-Tronconi B, Costa E, Guidotti A. Study of an octadecaneuropeptide derived from diazepam binding inhibitor (DBI): biological activity and presence in rat brain. Proc Natl Acad Sci USA 1986; 83(3): 827-31.
[http://dx.doi.org/10.1073/pnas.83.3.827] [PMID: 3456171]
[36]
Slobodyansky E, Guidotti A, Wambebe C, Berkovich A, Costa E. Isolation and characterization of a rat brain triakontatetraneuropeptide, a posttranslational product of diazepam binding inhibitor: specific action at the Ro 5-4864 recognition site. J Neurochem 1989; 53(4): 1276-84.
[http://dx.doi.org/10.1111/j.1471-4159.1989.tb07425.x] [PMID: 2769267]
[37]
Papadopoulos V, Berkovich A, Krueger KE, Costa E, Guidotti A. Diazepam binding inhibitor and its processing products stimulate mitochondrial steroid biosynthesis via an interaction with mitochondrial benzodiazepine receptors. Endocrinology 1991; 129(3): 1481-8.
[http://dx.doi.org/10.1210/endo-129-3-1481] [PMID: 1651852]
[38]
Li H, Degenhardt B, Tobin D, Yao Z-X, Tasken K, Papadopoulos V. Identification, localization, and function in steroidogenesis of PAP7: a peripheral-type benzodiazepine receptor- and PKA (RIalpha)-associated protein. Mol Endocrinol 2001; 15(12): 2211-28.
[PMID: 11731621]
[39]
Fan J, Liu J, Culty M, Papadopoulos V. Acyl-coenzyme A binding domain containing 3 (ACBD3; PAP7; GCP60): an emerging signaling molecule. Prog Lipid Res 2010; 49(3): 218-34.
[http://dx.doi.org/10.1016/j.plipres.2009.12.003] [PMID: 20043945]
[40]
Liu J, Rone MB, Papadopoulos V. Protein-protein interactions mediate mitochondrial cholesterol transport and steroid biosynthesis. J Biol Chem 2006; 281(50): 38879-93.
[http://dx.doi.org/10.1074/jbc.M608820200] [PMID: 17050526]
[41]
Braestrup C, Squires RF. Specific benzodiazepine receptors in rat brain characterized by high-affinity (3H)diazepam binding. Proc Natl Acad Sci USA 1977; 74(9): 3805-9.
[http://dx.doi.org/10.1073/pnas.74.9.3805] [PMID: 20632]
[42]
Gavioli EC, Duarte FS, Bressan E, Ferrara P, Farges RC, De Lima TC. Antidepressant-like effect of Ro5-4864, a peripheral-type benzodiazepine receptor ligand, in forced swimming test. Eur J Pharmacol 2003; 471(1): 21-6.
[http://dx.doi.org/10.1016/S0014-2999(03)01789-8] [PMID: 12809948]
[43]
Barron AM, Garcia-Segura LM, Caruso D, et al. Ligand for translocator protein reverses pathology in a mouse model of Alzheimer’s disease. J Neurosci 2013; 33(20): 8891-7.
[http://dx.doi.org/10.1523/JNEUROSCI.1350-13.2013] [PMID: 23678130]
[44]
Mills C, Makwana M, Wallace A, et al. Ro5-4864 promotes neonatal motor neuron survival and nerve regeneration in adult rats. Eur J Neurosci 2008; 27(4): 937-46.
[http://dx.doi.org/10.1111/j.1460-9568.2008.06065.x] [PMID: 18333964]
[45]
Leonelli E, Yague JG, Ballabio M, et al. Ro5-4864, a synthetic ligand of peripheral benzodiazepine receptor, reduces aging-associated myelin degeneration in the sciatic nerve of male rats. Mech Ageing Dev 2005; 126(11): 1159-63.
[http://dx.doi.org/10.1016/j.mad.2005.06.001] [PMID: 16045970]
[46]
Soustiel JF, Zaaroor M, Vlodavsky E, Veenman L, Weizman A, Gavish M. Neuroprotective effect of Ro5-4864 following brain injury. Exp Neurol 2008; 214(2): 201-8.
[http://dx.doi.org/10.1016/j.expneurol.2008.08.008] [PMID: 18789929]
[47]
Veiga S, Azcoitia I, Garcia-Segura LM. Ro5-4864, a peripheral benzodiazepine receptor ligand, reduces reactive gliosis and protects hippocampal hilar neurons from kainic acid excitotoxicity. J Neurosci Res 2005; 80(1): 129-37.
[http://dx.doi.org/10.1002/jnr.20430] [PMID: 15696538]
[48]
Giatti S, Pesaresi M, Cavaletti G, et al. Neuroprotective effects of a ligand of translocator protein-18 kDa (Ro5-4864) in experimental diabetic neuropathy. Neuroscience 2009; 164(2): 520-9.
[http://dx.doi.org/10.1016/j.neuroscience.2009.08.005] [PMID: 19665520]
[49]
Le Fur G, Perrier ML, Vaucher N, Imbault F, Flamier A, Benavides J, et al. Peripheral benzodiazepine binding sites: effect of PK 11195, 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide I. In vitro studies. Life Sci 1983; 32(16): 1839-47.
[50]
Selleri S, Bruni F, Costagli C, et al. 2-Arylpyrazolo[1,5-a]pyrimidin-3-yl acetamides. New potent and selective peripheral benzodiazepine receptor ligands. Bioorg Med Chem 2001; 9(10): 2661-71.
[http://dx.doi.org/10.1016/S0968-0896(01)00192-4] [PMID: 11557354]
[51]
Zhang L-M, Zhao N, Guo W-Z, et al. Antidepressant-like and anxiolytic-like effects of YL-IPA08, a potent ligand for the translocator protein (18 kDa). Neuropharmacology 2014; 81: 116-25.
[http://dx.doi.org/10.1016/j.neuropharm.2013.09.016] [PMID: 24067925]
[52]
Zhang L-M, Qiu Z-K, Zhao N, et al. Anxiolytic-like effects of YL-IPA08, a potent ligand for the translocator protein (18 kDa) in animal models of post-traumatic stress disorder. Int J Neuropsychopharmacol 2014; 17(10): 1659-69.
[http://dx.doi.org/10.1017/S1461145714000479] [PMID: 24763106]
[53]
Kozikowski AP, Ma D, Brewer J, et al. Chemistry, binding affinities, and behavioral properties of a new class of “antineophobic” mitochondrial DBI receptor complex (mDRC) ligands. J Med Chem 1993; 36(20): 2908-20.
[http://dx.doi.org/10.1021/jm00072a010] [PMID: 8411007]
[54]
Kita A, Kohayakawa H, Kinoshita T, et al. Antianxiety and antidepressant-like effects of AC-5216, a novel mitochondrial benzodiazepine receptor ligand. Br J Pharmacol 2004; 142(7): 1059-72.
[http://dx.doi.org/10.1038/sj.bjp.0705681] [PMID: 15249420]
[55]
Zivkovic B, Morel E, Joly D, Perrault G, Sanger DJ, Lloyd KG. Pharmacological and behavioral profile of alpidem as an anxiolytic. Synthelabo Recherche, LERS, Bagneux, France 1990; 23(3): 108-13.
[http://dx.doi.org/10.1055/s-2007-1014545]
[56]
Kaplan J-P, George P. US Patent 4382938 A,1983
[57]
Langer SZ, Arbilla S, Benavides J, Scatton B. Zolpidem and alpidem: two imidazopyridines with selectivity for omega 1- and omega 3-receptor subtypes. Adv Biochem Psychopharmacol 1990; 46: 61-72.
[PMID: 1981304]
[58]
Bourguignon JJ. Endogenous and synthetic ligands of mitochondrial benzodiazepine receptors: structure-affinity relationshipsPeripheral benzodiazepine receptors. London: Academic Press 1993; pp. 59-85.
[59]
Barki J, Larrey D, Pageaux G, Lamblin G, Gineston JL, Michel H. [Fatal subfulminant hepatitis during treatment with alpidem (Ananxyl)]. Gastroenterol Clin Biol 1993; 17(11): 872-4. PMID: 7908272
[60]
Baty V, Denis B, Goudot C, et al. [Hepatitis induced by alpidem (Ananxyl). Four cases, one of them fatal]. Gastroenterol Clin Biol 1994; 18(12): 1129-31.
[PMID: 7750686]
[61]
Ausset P, Malavialle P, Vallet A, et al. [Subfulminant hepatitis caused by alpidem and treated by liver transplantation]. Gastroenterol Clin Biol 1995; 19(2): 222-3.
[PMID: 7750714]
[62]
Fiorini I, Nacci V, Ciani SM, et al. Novel ligands specific for mitochondrial benzodiazepine receptors: 6-arylpyrrolo[2,1-d][1,5]benzothiazepine derivatives. Synthesis, structure-activity relationships, and molecular modeling studies. J Med Chem 1994; 37(10): 1427-38.
[http://dx.doi.org/10.1021/jm00036a007] [PMID: 8182701]
[63]
Greco G, Novellino E, Fiorini I, et al. A comparative molecular field analysis model for 6-arylpyrrolo[2,1-d] [1,5]benzothiazepines binding selectively to the mitochondrial benzodiazepine receptor. J Med Chem 1994; 37(24): 4100-8.
[http://dx.doi.org/10.1021/jm00050a007] [PMID: 7990110]
[64]
Campiani G, Nacci V, Fiorini I, et al. New pyrrolobenzothiazepine derivatives as molecular probes of the “peripheral-type” benzodiazepine receptor (PBR) binding site. Eur J Med Chem 1997; 32: 241-52.
[http://dx.doi.org/10.1016/S0223-5234(97)83975-X]
[65]
Campiani G, Ramunno A, Fiorini I, et al. Synthesis of new molecular probes for investigation of steroid biosynthesis induced by selective interaction with peripheral type benzodiazepine receptors (PBR). J Med Chem 2002; 45(19): 4276-81.
[http://dx.doi.org/10.1021/jm020849l] [PMID: 12213069]
[66]
Okuyama S, Chaki S, Yoshikawa R, et al. Neuropharmacological profile of peripheral benzodiazepine receptor agonists, DAA1097 and DAA1106. Life Sci 1999; 64(16): 1455-64.
[http://dx.doi.org/10.1016/S0024-3205(99)00079-X] [PMID: 10321725]
[67]
Okubo T, Yoshikawa R, Chaki S, Okuyama S, Nakazato A. Design, synthesis and structure-affinity relationships of aryloxyanilide derivatives as novel peripheral benzodiazepine receptor ligands. Bioorg Med Chem 2004; 12(2): 423-38.
[http://dx.doi.org/10.1016/j.bmc.2003.10.050] [PMID: 14723961]
[68]
Chaki S, Funakoshi T, Yoshikawa R, et al. Binding characteristics of [3H]DAA1106, a novel and selective ligand for peripheral benzodiazepine receptors. Eur J Pharmacol 1999; 371(2-3): 197-204.
[http://dx.doi.org/10.1016/S0014-2999(99)00118-1] [PMID: 10357257]
[69]
Briard E, Zoghbi SS, Siméon FG, et al. Single-step high-yield radiosynthesis and evaluation of a sensitive 18F-labeled ligand for imaging brain peripheral benzodiazepine receptors with PET. J Med Chem 2009; 52(3): 688-99.
[http://dx.doi.org/10.1021/jm8011855] [PMID: 19119848]
[70]
Kita A, Furukawa K. Involvement of neurosteroids in the anxiolytic-like effects of AC-5216 in mice. Pharmacol Biochem Behav 2008; 89(2): 171-8.
[http://dx.doi.org/10.1016/j.pbb.2007.12.006] [PMID: 18201755]
[71]
Kita A, Kinoshita T, Kohayakawa H, Furukawa K, Akaike A. Lack of tolerance to anxiolysis and withdrawal symptoms in mice repeatedly treated with AC-5216, a selective TSPO ligand. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33(6): 1040-5.
[http://dx.doi.org/10.1016/j.pnpbp.2009.05.018] [PMID: 19497344]
[72]
Rupprecht R, Rammes G, Eser D, et al. Translocator protein (18 kD) as target for anxiolytics without benzodiazepine-like side effects. Science 2009; 325(5939): 490-3.
[http://dx.doi.org/10.1126/science.1175055] [PMID: 19541954]
[73]
Qiu Z-K, Zhang L-M, Zhao N, et al. Repeated administration of AC-5216, a ligand for the 18 kDa translocator protein, improves behavioral deficits in a mouse model of post-traumatic stress disorder. Prog Neuropsychopharmacol Biol Psychiatry 2013; 45: 40-6.
[http://dx.doi.org/10.1016/j.pnpbp.2013.04.010] [PMID: 23624119]
[74]
Wolf L, Bauer A, Melchner D, et al. Enhancing neurosteroid synthesis-relationship to the pharmacology of translocator protein (18 kDa) (TSPO) ligands and benzodiazepines. Pharmacopsychiatry 2015; 48(2): 72-7.
[http://dx.doi.org/10.1055/s-0034-1398507] [PMID: 25654303]
[75]
Wang D-S, Tian Z, Guo Y-Y, et al. Anxiolytic-like effects of translocator protein (TSPO) ligand ZBD-2 in an animal model of chronic pain. Mol Pain 2015; 11: 16.
[http://dx.doi.org/10.1186/s12990-015-0013-6] [PMID: 25889665]
[76]
Li XB, Guo HL, Shi TY, et al. Neuroprotective effects of a novel translocator protein (18 kDa) ligand, ZBD-2, against focal cerebral ischemia and NMDA-induced neurotoxicity. Clin Exp Pharmacol Physiol 2015; 42(10): 1068-74.
[http://dx.doi.org/10.1111/1440-1681.12460] [PMID: 26174423]
[77]
Fukaya T, Kodo T, Ishiyama T, et al. Design, synthesis and structure-activity relationships of novel benzoxazolone derivatives as 18 kDa translocator protein (TSPO) ligands. Bioorg Med Chem 2012; 20(18): 5568-82.
[http://dx.doi.org/10.1016/j.bmc.2012.07.023] [PMID: 22884355]
[78]
Anzini M, Cappelli A, Vomero S, et al. Mapping and fitting the peripheral benzodiazepine receptor binding site by carboxamide derivatives. Comparison of different approaches to quantitative ligand-receptor interaction modeling. J Med Chem 2001; 44(8): 1134-50.
[http://dx.doi.org/10.1021/jm0009742] [PMID: 11312914]
[79]
Cappelli A, Pericot Mohr Gl, Gallelli A, et al. Structure-activity relationships in carboxamide derivatives based on the targeted delivery of radionuclides and boron atoms by means of peripheral benzodiazepine receptor ligands. J Med Chem 2003; 46(17): 3568-71.
[http://dx.doi.org/10.1021/jm034068b] [PMID: 12904061]
[80]
Castellano S, Taliani S, Viviano M, et al. Structure-activity relationship refinement and further assessment of 4-phenylquinazoline-2-carboxamide translocator protein ligands as antiproliferative agents in human glioblastoma tumors. J Med Chem 2014; 57(6): 2413-28.
[http://dx.doi.org/10.1021/jm401721h] [PMID: 24580635]
[81]
Trapani G, Franco M, Ricciardi L, et al. Synthesis and binding affinity of 2-phenylimidazo[1,2-alpha]pyridine derivatives for both central and peripheral benzodiazepine receptors. A new series of high-affinity and selective ligands for the peripheral type. J Med Chem 1997; 40(19): 3109-18.
[http://dx.doi.org/10.1021/jm970112+] [PMID: 9301675]
[82]
Lentini G, Bourguignon JJ, Wermuth CG. Ligands of the peripheral-type benzodiazepine bindimg site (PBS): structureactivity relationships and computer-aided conformational analysisQASAR: Rational Approaches to the Design of Bioactive Compounds. Amsterdam: Elsevier Science Publishers B.V. 1991; pp. 257-60.
[83]
Tebib S, Bourguignon JJ, Wermuth CG. The active analog approach applied to the pharmacophore identification of benzodiazepine receptor ligands. J Comput Aided Mol Des 1987; 1(2): 153-70.
[http://dx.doi.org/10.1007/BF01676959] [PMID: 2848099]
[84]
Serra M, Madau P, Chessa MF, et al. 2-Phenyl-imidazo[1,2-a]pyridine derivatives as ligands for peripheral benzodiazepine receptors: stimulation of neurosteroid synthesis and anticonflict action in rats. Br J Pharmacol 1999; 127(1): 177-87.
[http://dx.doi.org/10.1038/sj.bjp.0702530] [PMID: 10369471]
[85]
James ML, Fulton RR, Vercoullie J, et al. DPA-714, a new translocator protein-specific ligand: synthesis, radiofluorination, and pharmacologic characterization. J Nucl Med 2008; 49(5): 814-22.
[http://dx.doi.org/10.2967/jnumed.107.046151] [PMID: 18413395]
[86]
Leaver KR, Reynolds A, Bodard S, Guilloteau D, Chalon S, Kassiou M. Effects of translocator protein (18 kDa) ligands on microglial activation and neuronal death in the quinolinic-acid-injected rat striatum. ACS Chem Neurosci 2012; 3(2): 114-9.
[http://dx.doi.org/10.1021/cn200099e] [PMID: 22860181]
[87]
Romeo E, Auta J, Kozikowski AP, et al. 2-Aryl-3-indoleacetamides (FGIN-1): a new class of potent and specific ligands for the mitochondrial DBI receptor (MDR). J Pharmacol Exp Ther 1992; 262(3): 971-8.
[PMID: 1326631]
[88]
Auta J, Romeo E, Kozikowski A, Ma D, Costa E, Guidotti A. Participation of mitochondrial diazepam binding inhibitor receptors in the anticonflict, antineophobic and anticonvulsant action of 2-aryl-3-indoleacetamide and imidazopyridine derivatives. J Pharmacol Exp Ther 1993; 265(2): 649-56.
[PMID: 8098760]
[89]
Bitran D, Foley M, Audette D, Leslie N, Frye CA. Activation of peripheral mitochondrial benzodiazepine receptors in the hippocampus stimulates allopregnanolone synthesis and produces anxiolytic-like effects in the rat. Psychopharmacology (Berl) 2000; 151(1): 64-71.
[http://dx.doi.org/10.1007/s002130000471] [PMID: 10958118]
[90]
Da Settimo F, Simorini F, Taliani S, et al. Anxiolytic-like effects of N,N-dialkyl-2-phenylindol-3-ylglyoxylamides by modulation of translocator protein promoting neurosteroid biosynthesis. J Med Chem 2008; 51(18): 5798-806.
[http://dx.doi.org/10.1021/jm8003224] [PMID: 18729350]
[91]
Costa B, Da Pozzo E, Chelli B, et al. Anxiolytic properties of a 2-phenylindolglyoxylamide TSPO ligand: Stimulation of in vitro neurosteroid production affecting GABAA receptor activity. Psychoneuroendocrinology 2011; 36(4): 463-72.
[http://dx.doi.org/10.1016/j.psyneuen.2010.07.021] [PMID: 20728278]
[92]
Liao Y, Kozikowski AP, Guidotti A, Costa E. Synthesis and pharmacological evaluation of benzofuran-acetamides as “antineophobic” mitochondrial DBI receptor complex ligands. Bioorg Med Chem Lett 1998; 8(16): 2099-102.
[http://dx.doi.org/10.1016/S0960-894X(98)00374-6] [PMID: 9873493]
[93]
Ferzaz B, Brault E, Bourliaud G, et al. SSR180575 (7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide), a peripheral benzodiazepine receptor ligand, promotes neuronal survival and repair. J Pharmacol Exp Ther 2002; 301(3): 1067-78.
[http://dx.doi.org/10.1124/jpet.301.3.1067] [PMID: 12023539]
[94]
Anzini M, Cappelli A, Vomero S, et al. Molecular basis of peripheral vs central benzodiazepine receptor selectivity in a new class of peripheral benzodiazepine receptor ligands related to alpidem. J Med Chem 1996; 39(21): 4275-84.
[http://dx.doi.org/10.1021/jm960325j] [PMID: 8863805]
[95]
Cappelli A, Giuliani G, Valenti S, et al. Synthesis and structure-activity relationship studies in peripheral benzodiazepine receptor ligands related to alpidem. Bioorg Med Chem 2008; 16(6): 3428-37.
[http://dx.doi.org/10.1016/j.bmc.2007.06.044] [PMID: 18294852]
[96]
Cappelli A, Bini G, Valenti S, et al. Synthesis and structure-activity relationship studies in translocator protein ligands based on a pyrazolo[3,4-b]quinoline scaffold. J Med Chem 2011; 54(20): 7165-75.
[http://dx.doi.org/10.1021/jm200770f] [PMID: 21916402]
[97]
Schlichter R, Rybalchenko V, Poisbeau P, Verleye M, Gillardin J. Modulation of GABAergic synaptic transmission by the non-benzodiazepine anxiolytic etifoxine. Neuropharmacology 2000; 39(9): 1523-35.
[http://dx.doi.org/10.1016/S0028-3908(99)00253-1] [PMID: 10854897]
[98]
Verleye M, Akwa Y, Liere P, et al. The anxiolytic etifoxine activates the peripheral benzodiazepine receptor and increases the neurosteroid levels in rat brain. Pharmacol Biochem Behav 2005; 82(4): 712-20.
[http://dx.doi.org/10.1016/j.pbb.2005.11.013] [PMID: 16388839]
[99]
Ugale RR, Sharma AN, Kokare DM, Hirani K, Subhedar NK, Chopde CT. Neurosteroid allopregnanolone mediates anxiolytic effect of etifoxine in rats. Brain Res 2007; 1184: 193-201.
[http://dx.doi.org/10.1016/j.brainres.2007.09.041] [PMID: 17950705]
[100]
Aouad M, Charlet A, Rodeau JL, Poisbeau P. Reduction and prevention of vincristine-induced neuropathic pain symptoms by the non-benzodiazepine anxiolytic etifoxine are mediated by 3alpha-reduced neurosteroids. Pain 2009; 147(1-3): 54-9.
[http://dx.doi.org/10.1016/j.pain.2009.08.001] [PMID: 19786322]
[101]
Nguyen N, Fakra E, Pradel V, et al. Efficacy of etifoxine compared to lorazepam monotherapy in the treatment of patients with adjustment disorders with anxiety: a double-blind controlled study in general practice. Hum Psychopharmacol 2006; 21(3): 139-49.
[http://dx.doi.org/10.1002/hup.757] [PMID: 16625522]
[102]
Zanetta C, Nizzardo M, Simone C, et al. Molecular therapeutic strategies for spinal muscular atrophies: current and future clinical trials. Clin Ther 2014; 36(1): 128-40.
[http://dx.doi.org/10.1016/j.clinthera.2013.11.006] [PMID: 24360800]
[103]
Schaller S, Paradis S, Ngoh GA, et al. TRO40303, a new cardioprotective compound, inhibits mitochondrial permeability transition. J Pharmacol Exp Ther 2010; 333(3): 696-706.
[http://dx.doi.org/10.1124/jpet.110.167486] [PMID: 20215409]
[104]
Mokrov GV, Deeva OA, Gudasheva TA, Yarkov SA, Yarkova MA, Seredenin SB. Design, synthesis and anxiolytic-like activity of 1-arylpyrrolo[1,2-a]pyrazine-3-carboxamides. Bioorg Med Chem 2015; 23(13): 3368-78.
[http://dx.doi.org/10.1016/j.bmc.2015.04.049] [PMID: 25937237]
[105]
Baraboshkin NM, Pantileev AS, Mokrov GV. Approaches to predict ligands affinity towards translocator protein TSPO 18 kDa in order to create molecules possessing neuropsychotropic activity Baraboshkin 2019; 1: 22-30.
[106]
Seredenin SB, Mokrov GV, Gudasheva TA, et al. 1-Arylpyrrolo[1,2-a]pyrazine-3-carboxamides with neuropsychotropic activity RF patent no. 2572076, 2014.
[107]
Yarkov SA, Mokrov GV, Gudasheva TA, et al. Pharmacological study of new compounds acting as regulators of 18-kDa translocator protein ligands Experimentalnaya i klinicheskaya farmakologiya 2016; 79(1): 7-11.
[108]
Yarkova MA, Mokrov GV, Gudasheva TA, et al. Novel Pyrrolo[1,2-a]pyrazines (TSPO Ligands) with Anxiolytic Activity Dependent on Neurosteroid Biosynthesis. Pharm Chem J 2016; 50: 501-4.
[http://dx.doi.org/10.1007/s11094-016-1476-0]
[109]
Yarkova MA, Povarnina PYu, Mokrov GV, et al. Antidepressant and nootrope effects of original TSPO ligands Experimentalnaya i klinicheskaya farmakologiya 2017; 80(4): 3-7.
[110]
Novitsky AA, Bochkov PO, Shevchenko RV, et al. .Pharmacokinetics of potential anxiolytic GML-1 in rats. Experimentalnaya i klinicheskaya farmakologiya 2018; 81(6): 24-8.
[111]
Yarkova MA, Blynskaya EV, Yudina DV, et al. Development and Study of Anxiolytic Effect of Gml-1 Tablet Dosage Form. Pharm Chem J 2019; 53: 342-6.
[http://dx.doi.org/10.1007/s11094-019-02003-1]
[112]
Gudasheva TA, Deeva OA, Mokrov GV, Yarkov SA, Yarkova MA, Seredenin SB. The first dipeptide ligand of translocator protein: Design and anxiolytic activity. Dokl Biochem Biophys 2015; 464: 290-3.
[http://dx.doi.org/10.1134/S1607672915050063] [PMID: 26518550]
[113]
Seredenin SB, Deeva OA, Gudasheva TA, et al. Substituted dipeptides with neuropsychotropic activity RF Patent no. 2573823, 2014.
[114]
Gudasheva TA. Theoretical grounds and technologies for dipeptide drug development. Russian Chem Bulletin Inter Ed 2015; 64: (9): 2012-21. http://dx.doi.org/10.1007/s11172-015-1112-2
[115]
Gudasheva TA, Voronina TA, Ostrovskaya RU, et al. Design of N-acylprolyltyrosine “tripeptoid” analogues of neurotensin as potential atypical antipsychotic agents. J Med Chem 1998; 41(3): 284-90.
[http://dx.doi.org/10.1021/jm970217c] [PMID: 9464359]
[116]
Gudasheva TA. Strategy for the development of dipeptide drugs. Vestnik RAMN 2011; 7: 8-16.
[117]
Gudasheva TA, Deeva OA, Mokrov GV, Dyabina AS, Yarkova MA, Seredenin SB. Design, Synthesis and Anxiolytic Activity Evaluation of N-Acyltryptophanyl- Containing Dipeptides, Potential TSPO Ligands. Med Chem 2019; 15(4): 383-99.
[http://dx.doi.org/10.2174/1573406415666181119164846] [PMID: 30457052]
[118]
Gudasheva TA, Deeva OA, Yarkova MA, Seredenin SB. Dependence of anxiolytic effects of the dipeptide TSPO ligand GD-23 on neurosteroid biosynthesis. Dokl Biochem Biophys 2016; 469(1): 298-301.
[http://dx.doi.org/10.1134/S1607672916040165] [PMID: 27599516]
[119]
Povarnina PY, Yarkov SA, Gudasheva TA, Yarkova MA, Seredenin SB. The Novel Dipeptide Translocator Protein Ligand, Referred to As GD-23, Exerts Anxiolytic and Nootropic Activities. Acta Naturae 2015; 7(3): 108-12.
[http://dx.doi.org/10.32607/20758251-2015-7-3-108-112] [PMID: 26483966]
[120]
Deeva OA, Pantileev AS, Rybina IV, Yarkova MA, Gudasheva TA, Seredenin SB. A novel dipeptide ligand of TSPO. Dokl Biochem Biophys 2019; 484(1): 17-20.
[http://dx.doi.org/10.1134/S1607672919010046] [PMID: 31012004]
[121]
Deeva OA, Pantileev AS, Rebeko AG, et al. Synthesis and structure - anxiolytic activity relationship analysis for leucyltriptophane ligands of 18 kDa translocator protein. Khim Farm Zh 2020; 54(6): 24-34.

Rights & Permissions Print Cite
Article Metrics
60
Wayfinder Image
Open Access Journals Promotions
World Antimicrobial Awareness Week
© 2024 Bentham Science Publishers | Privacy Policy