Translocator Protein TSPO (Peripheral Benzodiazepine Receptor): The Modern Story of the Ancient Preserved Protein with Ambiguous Functions

Authors

  • Yassir Mustafa Kamal Al Mulla Hummadi Department of Pharmacology and Toxicology, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq.

DOI:

https://doi.org/10.31351/vol33iss1pp1-10

Keywords:

Keywords: peripheral benzodiazepine receptors, translocator protein TSPO, steroidogenic acute regulatory protein StAR, cholesterol, mitochondria, central benzodiazepine receptor CBR, peripheral benzodiazepine receptor PBR

Abstract

In several tissues, including the brain, heart, blood, intestines, adrenal glands, and liver, the 18 kDa translocator protein (TSPO) was shown to be the peripheral benzodiazepine receptor. There is strong evidence that TSPO is expressed in microglial cells in the central nervous system. Five transmembrane regions are seen at the cellular level in TSPO at the contact points between the outer and inner layers of mitochondria. The cytosolic region of the complex of amino acids that binds cholesterol is where cholesterol is taken up. TSPO is found as a monomer of 18 kDa and homomultimers and homodimers. Different factors, such as cholesterol concentration and reactive oxygen species, change the multimeric structure. As a result, TSPO gains responsibility for transferring cholesterol to the mitochondrial intermembrane space, transforming it into a steroid. Additionally, TSPO appears to collaborate with other mitochondrial membrane proteins to play a part in regulating the activity of the MPTP (mitochondrial permeability transition pore) and, therefore, in the elements of apoptosis. In vivo imaging of TSPO addresses a significant test in examining brain pathology like neuroinflammatory, Alzheimer’s, and schizophrenia. Additionally, TSPO’s use as a biomarker may have important implications for developing more viable diagnostic and therapeutic approaches. The current work surveys the TSPO cellular origin and attempts to comprehend its role in various physiological and pathological conditions.

How to Cite

1.
Al Mulla Hummadi YMK. Translocator Protein TSPO (Peripheral Benzodiazepine Receptor): The Modern Story of the Ancient Preserved Protein with Ambiguous Functions. Iraqi Journal of Pharmaceutical Sciences [Internet]. 2024 Mar. 26 [cited 2024 Dec. 5];33(1):1-10. Available from: https://bijps.uobaghdad.edu.iq/index.php/bijps/article/view/2303

Publication Dates

References

Mokrov GV, Deeva OA and Gudasheva TA. The ligands of translocator protein: design and biological properties, Curr Pharm Des.2021; 27 (2): 217–37. doi:10.2174/ 1 3 8 1 61 2826666 2009 03122025 . P M I D 3 2 881658.

Jaremko Ł, Jaremko M, Giller K, et al. structure of the mitochondrial translocator protein in complex with a diagnostic ligand. Science.2014; 343(6177): 1363- 66. DOI: 10.1126/science.1248725.

Bogan RL, Davis TL, Niswender GD , Peripheral-type benzodiazepine receptor (PBR) aggregation and absence of steroidogenic acute regulatory protein (StAR)/PBR association in the mitochondrial membrane as determined by bioluminescence resonance energy transfer (BRET), J. Steroid Biochem. Mol. Biol. 2007; 104 (1–2): 61–7. doi: 10.1016/j.jsbmb.2006.10.007. PMID 17197174. S2CID 24634653.

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.

Snyder, S. H. The peripheral-type benzodiazepine receptor. Localization to the mitochondrial outer membrane, J. Biol. Chem. 1989; 261(2): 576–83.

Li F, Liu J, Zheng Y, Garavito RM and Ferguson-Miller S, Crystal structures of translocator protein (TSPO) and mutant mimic of a human polymorphism. Science. 2015; 350(6260): 519-c.

Guo Y, Kalathur RC, Liu Q et al. Structure and activity of tryptophan-rich TSPO proteins. Science. 2015; 347(6221): 551-55. DOI: 10.1126/science.aaa1534

Veenman L, Vainshtein A, and Yasin N, et al. Tetrapyrroles as endogenous TSPO ligands in eukaryotes and prokaryotes: Comparisons with synthetic ligands, Int J Mol Sci. 2016; 17(6): 880. DOI:10 .3390/ ijms17060880

Joseph-Liauzun E, Delmas P and Shire D, et al. Topological analysis of the peripheral benzodiazepine receptor in yeast mitochondrial membranes supports a five-transmembrane structure, J. Biol. Chem.1998; 273(4): 2146–52.

McEnery MW, Snowman AM and Trifiletti RR, et al. Isolation of the mitochondrial benzodiazepine receptor: association with the voltage dependent anion channel and the adenine nucleotide carrier, Proc. Natl Acad. Sci. USA. 1992; 89(8): 3170–74.

Garnier M, Dimchev AB. and Boujrad N., et al. In vitro reconstitution of a functional peripheral-type benzodiazepine receptor from mouse Leydig tumor cells, Mol. Pharmacol. 1994; 45:201–11.

Veenman L, Shandalov Y and Gavish M, VDAC activation by the 18 kDa translocator protein (TSPO), implications for apoptosis, J. Bioenerg. Biomembr. 2008; 40(3): 199–205. DOI: 10 .1007 /s10863 -008-9142-1.

Arnold K, Bordoli L and Kopp J, et al. The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling, Bioinformatics. 2006; 22(2): 195–201. DOI: 10.1093/ bioinformatics/bti770

Schmidt O, Rahman M and Ma G, et al. Mode of action of antimicrobial proteins, pore-forming toxins and biologically active peptides (Hypothesis), Invertebrate Surv. J. 2005; 2(2): 82–90.

Wang J, Sykes BD and Ryan RO, Structural basis for the conformational adaptability of apolipophorin III, a helix-bundle exchangeable apolipoprotein, Proc. Natl Acad. Sci. USA. 2002; 99: 1188–93. DOI: 10.1073/pnas.032565999

Culty M, Li H and Boujrad N, et al. In vitro studies on the role of the peripheral-type benzodiazepine receptor in steroidogenesis, J. Steroid. Biochem. Mol. Biol. 1999; 69(1-6); 123–30. doi.org/ 10.1016/ S0960-0760(99)00056-4

Delavoie F, Li H and Hardwick M, et al. In vivo and in vitro peripheral-type benzodiazepine receptor polymerization: functional significance in drug ligand and cholesterol binding, Biochemistry. 2003; 42:4506–19.

Lacapere JJ and 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. DOI: 10.1016/s0039-128x(03)00101-6

Baestrup C and Squires RF, Specific benzodiazepine receptors in rat brain characterized by high-affinity [3H]-diazepam binding, Proc Nat Acad Sci. 1977; 74(9): 3805–9. [PubMed: 20632].

Maragos PJ, Patel J and Boulenger JP, et al, characterization of peripheral-type benzodiazepine binding sites in brain using [3H]-Ro5–4864, Mol Pharmacol. 1982; 22(1): 26–32. [PubMed: 6289073]

Patel J and Marangos PJ, Differential effects of GABA on peripheral and central type benzodiazepine binding sites in brain, Neurosci Lett. 1982; 30(2): 157–60. [PubMed: 6287365]

Benavides J, Quarteronet D and Imbault F, et al. Labelling of “peripheral-type” benzodiazepine binding sites in the rat brain by using [3H]-PK11195, an isoquinoline carboxamide derivative: kinetic studies and autoradiographic localization, J Neurochem. 1983; 41(6):1744–50. [PubMed: 6315880]

Anholt RRH, Pedersen PL and De Suoza EB, et al. The peripheral-type benzodiazepine receptor-localization to the mitochondrial outer membrane, J Biol Chem. 1986; 261(2): 576–83. [PubMed: 3001071]

Schoemaker H, Morelli M and Deshmukh P, etal. [3H]-Ro5–4864 benzodiazepine binding in the kainate lesioned striatum and Huntington’s disease basal ganglia, Brain Res.1982; 248(2): 396–401. [PubMed: 6291702] DOI: 10.1016/0006-8993(82) 90602 -3

Starosta-Rubenstein S, Ciliax BJ and Penney JB, et al. Imaging of a glioma using peripheral benzodiazepine receptor ligands, Proc Nat Acad Sci. 1987; 84(3): 891–895. [PubMed: 3027710]

Junck L, Olson JMM and Ciliax BJ, et al. PET imaging of human gliomas with ligands for the peripheral benzodiazepine binding site, Ann Neurol. 1989; 26(6): 752–8. [PubMed: 2557794]

Gehlert DR, Yamamura HI and Wamsley JK, Autoradiographic localization of “peripheral-type” benzodiazepine binding sites in the rat brain, heart, and kidney, Naunyn Schmiedebergs Arch Pharmacol.1985; 328(4): 454–60. [PubMed: 2986017]

Doble A, Malgouris C and Daniel M, et al. Labelling of peripheral-type benzodiazepine binding sites in human brain using [3H]-PK11195: anatomical and subcellular distribution, Brain Res Bull.1987; 18(1): 49–61. [PubMed: 3030512]

Benavides J, Fage D and Carter C, Peripheral type benzodiazepine binding sites are a sensitive indirect index of neuronal damage, Brain Res.1987; 421(1-2): 167–72. [PubMed: 2891401]

Dubois A, Benavides J and Peny B, et al. Imaging of primary and remote ischaemic and excitotoxic brain lesions. An autoradiographic study of peripheral type benzodiazepine binding sites in the rat and cat, Brain Res.1988; 445(1): 77–90. [PubMed: 2835123]

Benavides J, Cornu P and Dennis T, et al. Imaging of human brain lesions with an omega 3 site radioligand, Ann Neurol.1988; 24(6): 708–712. [PubMed: 2849920]

Benavides J, Dubois A and Gotti B, etal. Cellular distribution of omega 3 (peripheral type benzodiazepine) binding sites in the normal and ischaemic rat brain: an autoradiographic study with the photoaffinity ligand [3H]-PK14105 Neurosci Lett. 1990; 114(1): 32–38. [PubMed: 2166260]

Diorio D, Welner SA and Butterworth RF, et al. Peripheral benzodiazepine binding sites in Alzheimer’s disease frontal cortex and temporal cortex, Neurobiol. Aging. 1991; 12(3): 255–258. [PubMed: 1652108]

Miyazawa N, Diksic M and Yamamoto Y, Chronological study of peripheral benzodiazepine binding sites in the rat stab wounds using [3H]-PK11195 as a marker of gliosis, Acta Neurochir (Wien).1995; 137(3-4): 207–216. [PubMed: 8789663]

Guilarte TR, Kuhlmann AC and O’Callaghan JP, et al. Enhanced expression of peripheral benzodiazepine receptors in the trimethyltin-exposed rat brain: a biomarker of neurotoxicity, Neurotoxicol.1995; 16(3): 441–50.

Krueger KE and Papadopoulos V, Peripheral-type benzodiazepine receptors mediate translocation of cholesterol from outer to inner mitochondrial membranes in adrenocortical cells, J Biol Chem. 1990; 265(25): 15015–22. [PubMed: 2168398]

Papadopoulos V, Baraldi M and 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. [PubMed: 16822554]

Morohaku K, Pelton SH and Daugherty DJ, et al, Translocator protein/peripheral benzodiazepine receptor is not required for steroid hormone biosynthesis, Endocrinol. 2014; 155(1): 89–97.

Tu LN, Zhao AH and Stocco DM et al, PK11195 effect on steroidogenesis is not mediated through the translocator protein (TSPO), Endocrinol. 2015; 156(3): 1033–39.

Fan J, Lindemann P and Feuilloley MGJ, et al Structural and functional evolution of the translocator protein (18 kDa), Curr Mol Med. 2012; 12(4): 369-86.

Yeliseev AA, Krueger KE and Kaplan S, A mammalian mitochondrial drug receptor functions as a bacterial “oxygen” sensor, Proc Natl Acad Sci U S A. 1997; 94(10): 5101-6.

Chapalain A, Chevalier S and Orange N, et al. Bacterial ortholog of mammalian translocator protein (TSPO) with virulence regulating activity, PLoS One. 2009; 4(6): e6096. DOI: 10. 1371/ journal. Pone .0006096

Riond J, Leplatois P and Laurent P, et al Expression and pharmacological characterization of the human peripheral type benzodiazepine receptor in yeast, Eur J Pharmacol. 1991; 208(4): 307-12. DOI: 10.1016/0922-4106(91)90076-t

Fan J, Rone MB and Papadopoulos V, Translocator protein 2 is involved in cholesterol redistribution during erythropoiesis, J Biol Chem. 2009; 284(44): 30484-97

Owen DR, Yeo AJ and 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.

Rupprecht R, Papadopoulos V and Rammes G, et al Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders, Nat Rev Drug Discov. 2010; Dec; 9(12):971-88. doi: 10.1038/nrd3295.

Casellas P, Galiegue S and Basile AS, Peripheral benzodiazepine receptors and mitochondrial function, Neurochem Int. 2002; 40 (6): 475–86. doi: 10.1016 /S0197 -0186 (01) 001188 PMID 11850104. S2CID 18428847

Lacapère JJ and 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. doi:10.1016/s0039-128x(03) 00 1 01 -6 PMID 12957662 .S2CID 26232 564.

Midzak A and Papadopoulos V, Binding domain-driven intracellular trafficking of sterols for synthesis of steroid hormones, bile acids and oxysterols, Traffic. 15 (9): 895–914. doi: 10.1111/ tra. 12177 PMID 24 890942. year?

Qi X, Xu J and Wang F, et al. Translocator protein (18 kDa): a promising therapeutic target and diagnostic tool for cardiovascular diseases, Oxid Med Cell Longev. 2012: 1–9. doi: 10. 1155 /2012 /162934. PMC 3516045. PMID 23251719.

Fairweather D, Coronado MJ and Garton AE, et al. Sex differences in translocator protein 18 kDa (TSPO) in the heart: implications for imaging myocardial inflammation, J Cardiovasc Transl Res. 2014; 7 (2): 192–202. doi:10. 1007/s12265 -013-9538-0 . PMC 395197 3. PMID 244 02571.

Wolf A, Herb M and Schramm M, et al, The TSPO-NOX1 axis controls phagocyte-triggered pathological angiogenesis in the eye, nature communications. 2020, 11(1) : 2709 . doi: 10. 1038 /s41467-020-16400 -8

Pawlikowski M, Immunomodulating effects of peripherally acting benzodiazepines, New York: In Peripheral Benzodiazepine Receptors. Academic press. 1993, pp. 125–135.

Ren H, Han R and Chen X, et al. Potential therapeutic targets for intracerebral hemorrhage-associated inflammation: An update, J Cereb Blood Flow Metab. 2020, 40 (9): 1752-1768. doi: 10.1177/ 0271678X20923551. PMC 7446 569 . P M ID 324 23330.

Batarseh A and Papadopoulos V, Regulation of translocator protein 18 kDa (TSPO) expression in health and disease states, Mol. Cell. Endocrinol. 2010, 327 (1–2): 1–12. doi:10.1016/j.mce.2010.06.013. PMC 2922062. PMID 20600583.

Tanimoto Y, Onishi Y and Sato Y, et al. Benzodiazepine receptor agonists modulate thymocyte apoptosis through reduction of the mitochondrial transmembrane potential, Jpn. J. Pharmacol. 1999; 79 (2): 177–83. doi:10.1254/jjp.79.177. PMID 10202853.

Frank W, Baar KM and Qudeimat E, et al, A mitochondrial protein homologous to the mammalian peripheral- type benzo- diazepine receptor is essential for stress adaptation in plants, Plant J. 2007; 51 (6): 1004–18. doi:10.1111/j.1365-313X. 2007. 03198.x. PMID 17651369.

Marangos PJ, Patel J and Boulenger JP, et al. characterization of peripheral-type benzodiazepine binding sites in brain using [3H]Ro 5-4864, Molecular Pharmacology. 1982; 22 (1): 26–32. PMID 6289073.

Valtier D, Malgouris C and Gilbert JC, et al. Binding sites for a peripheral type benzodiazepine antagonist ([3H] PK 11195) in human iris, Neuro-pharmacology . 1987; 26 (6): 549–52. doi:10.1016/0028-3908 (87) 90146-8 . PMID 3037422 . S2CI D 45 0 3 5355.

Woods MG and Williams DC, Multiple forms and locations for the peripheral-type benzodiazepine receptor, Biochemical Pharmacology. 1996; 52 (12): 1805–1814. doi:10.1016/S0006-2952(96)00558-8. PMID 8951338.

Chen MK and Guilarte TR, Translocator protein 18 kDa (TSPO): molecular sensor of brain injury and repair, Pharmacology & Therapeutics. 2008; 118 (1): 1–17. doi:10.1016/j.pharmthera.2007.12.004. PMC 2453598. PMID 18374421.

Santidrián AF, Cosialls AM and Coll-Mulet L, et al. The potential anticancer agent PK11195 induces apoptosis irrespective of p53 and ATM status in chronic lymphocytic leukemia cells”. Haematologica. 2007; 92 (12): 1631–8. doi: 10.3324/ haematol. 11194 .PMI D 18055986.

Kugler W, Veenman L and Shandalov Y, et al. Ligands of the mitochondrial 18 kDa translocator protein attenuate apoptosis of human glioblastoma cells exposed to erucylphosphohomocholine, Cellular Oncology. 2008; 30(5): 435–50 .doi :10 .3233 /clo -2008 - 0431. PM C 46 18834. PMID 18791274.

Veenman L, Papadopoulos V and Gavish M, Channel-like functions of the 18-kDa translocator protein (TSPO): regulation of apoptosis and steroidogenesis as part of the host-defense response, Current Pharmaceutical Design. 2007; 13 (23): 2385–405. doi: 10.2174/ 1381612 077813 68710 .PMID 17692008.

Mealy NE, Bayés M and Lupone B, Psychiatric Disorders, Drugs of the Future. 2006; 31(3): 259.

Falchi AM, Battetta B and Sanna F, et al. Intracellular cholesterol changes induced by translocator protein (18 kDa) TSPO/PBR ligands , Neuropharma-cology. 2007; 53 (2): 318–29. doi :10. 1016/ j. neuropharm .2007 .05. 016 . P MI D 176 31921. S2CID 39793765.

Farb DH and Ratner MH, Targeting the modulation of neural circuitry for the treatment of anxiety disorders, Pharmacol Rev. 2014; 66 (4): 1002–1032. doi: 10.1124/pr.114.009126. PMID 25237115. S2CID 14537740.

Barron AM, Garcia-Segura LM and Caruso D, et al. Ligand for Translocator Protein Reverses Pathology in a Mouse Model of Alzheimer’s Disease, The Journal of Neuroscience. 2013; 33 (20): 8891–8897 . doi:10. 1523 /JNEUROSCI.1350-13. 2013 . PMC 37 33563. PMID 23678130.

Da Settimo F, Simorini F and Taliani S, et al. Anxiolytic-like effects of N,N-dialkyl-2-phenylindol-3-ylglyoxylamides by modulation of translocator protein promoting neurosteroid biosynthesis , Journal of Medicinal Chemistry . 2008; 51 (18): 5798–806. doi: 10. 1021 /jm8003 224 . PMID 18 729350.

Taliani S, Da Settimo F and Da Pozzo E, et al. Translocator Protein Ligands as Promising Therapeutic Tools for Anxiety Disorders, Current Medicinal Chemistry . 2009; 16 (26): 3359–80. doi:10.2174 /092986709789057653. PMID 19548867.

Rupprecht R, Rammes G and Eser D, et al. Translocator Protein (18 kD) as Target for Anxiolytics Without Benzodiazepine-Like Side Effects, Science. 2009; 325 (5939): 490–3. Bibcode :2009Sci... 325 ..49 0R . doi:10.1126/ science. 117 5055 . P MI D 19 541954. S2CID 26125316.

Skolnick P, Anxioselective anxiolytics: on a quest for the Holy Grail, Trends Pharmacol Sci. 2012; 33 (11): 611–620. doi:10.1016/j .tips.2012. 08.003 . P M C3 4 82271. PMID 22981367.

Gavish M, Bachman I and Shoukrun R, et al. Enigma of the peripheral benzodiazepine receptor, Pharmacological Reviews. 1999; 51(4): 629–50 . PMID 10 5 81326.

Okubo T, Yoshikawa R and Chaki S, et al. Design, synthesis and structure-affinity relationships of aryloxyanilide derivatives as novel peripheral benzodiazepine receptor ligands, Bioorg Med Chem. 2004;12(2):423-38. doi: 10 .1016 / j.bmc . 2003.10.050. PMID: 14723961.

Kumata K, Zhang Y and Fujinaga M, et al. [18F] DAA1106: Automated radiosynthesis using spirocyclic iodonium ylide and preclinical evaluation for positron emission tomography imaging of translocator protein (18 kDa), Bioorg Med Chem. 2018; 26(17):4817-22. doi: 10.1016/j.bmc.2018.08.017. Epub 2018 Aug 12. PMID: 30166255.

Rodríguez-Chinchilla T, Quiroga-Varela A and Molinet-Dronda F, et al. [18F]-DPA-714 PET as a specific in vivo marker of early microglial activation in a rat model of progressive dopaminergic degeneration, Eur J Nucl Med Mol Imaging. 2020;47(11):2602-12. doi: 10.1007/s00259-020-04772-4. Epub 2020 Mar 23. PMID: 32206840.

Zhang H, Ma L and Guo WZ, et al. TSPO ligand etifoxine attenuates LPS-induced cognitive dysfunction in mice. Brain Res Bull. 2020; 165:178-84. doi: 10.1016/j.brainresbull.2020.10.013. Epub 2020 Oct 16. PMID: 33075418.

Dimitrova-Shumkovska J, Krstanoski L and Veenman L, Diagnostic and Therapeutic Potential of TSPO Studies Regarding Neurodegenerative Diseases, Psychiatric Disorders, Alcohol Use Disorders, Traumatic Brain Injury, and Stroke: An Update, Cells. 2020; 9(4):870. doi: 10.3390/cells9040870. PMID: 32252470; PMCID: PMC7226777.

Liu J, Rone MB and Papadopoulos V, et al. Protein–protein interactions mediate mitochondrial cholesterol transport and steroid biosynthesis, J. Biol. Chem. 2006; 281(50): 38879–93.

Lacor P, Gandolfo P and Tonon MC, et al. regulation of the expression of peripheral benzodiazepine receptors and their endogenous ligands during rat sciatic nerve degeneration and regeneration: a role for PBR in neurosteroidogenesis, Brain Res. 1999; 815(1):70-80. doi: 10.1016/s0006-8993(98)01105-6. PMID: 9974124.

Tokay T, Hachem R and Masmoudi-Kouki O, et al. Beta-amyloid peptide stimulates endozepine release in cultured rat astrocytes through activation of N-formyl peptide receptors, Glia. 2008; 56(13):1380-9. doi: 10.1002/glia.20705. PMID: 18512251.

Werry EL, Bright FM, and Piguet O, et al. Recent developments in TSPO PET imaging as a biomarker of neuroinflammation in neurodegenerative disorders. Int J Mol Sci. 2019; 20:3161.

Yokokura M, Terada T and Bunai T, et al. Depiction of microglial activation in aging and dementia: positron emission tomography with 11C-DPA713 versus 11C-(R) PK11195. J Cereb Blood Flow Metab. 2017; 37:877–889.

Fujita M, Kobayashi M and Ikawa M, et al. Comparison of four 11C-labeled PET ligands to quantify translocator protein 18 kDa (TSPO) in human brain: (R)-PK11195, PBR28, DPA-713, and ER176—based on recent publications that measured specific-to-non-displaceable ratios. EJNMMI Res. 2017;7:84.

Shang C, Guo Y, Yao J and Fang X, et al. Rapid anti-PTSD-like activity of the TSPO agonist YL-IPA08: Emphasis on brain GABA, neurosteroids and HPA axis function. Behavioural Brain Research.2020; 379: 112320, https:// doi.org / 10.1016/j.bbr.2019.112320.

Zhang L.-M., Qiu Z.-K. and Chen X.-F., et al. Involvement of allopregnanolone in the anti-PTSD-like effects of AC-5216. J. Psychopharmacol. (Oxford) 2016; 30:474–481. doi: 10.1177/ 0269881115 625115 . [PubMed] [CrossRef] [Google Scholar]

Zivkovic B, Morel E and Joly D, et al. Pharmacological and behavioral profile of Alpidem as an anxiolytic .Pharmacopsychiatry. 1990; 23(3): 108–13. Doi: 10. 1055 /s- 2007-1014545 PMID 197 4069.

Sanger DJ, Zivkovic B. Discriminative stimulus effects of Alpidem, a new imidazopyridine anxiolytic. Psycho-pharmacology. 1994; 113(3 – 4) :395 403. doi: 10.1007/ bf 02 245 21 5. PMID 7862851. S2CID 24375542.

Kita A, Kohayakawa H and Kinoshita T, et al. Antianxiety and antidepressant-like effects of AC-5216, a novel mitochondrial benzodiazepine receptor ligand. British Journal of Pharmacology. 2004; 142 (7): 1059–72. doi: 10.1038 /sj. bjp. 0705681 .PMC 1575165. PMID 15249420.

Pike VW, Halldin C and Crouzel C, et al. Radioligands for PET studies of central benzodiazepine receptors and PK (peripheral benzodiazepine) binding sites--current status. Nuclear Medicine and Biology.1993; 20 (4): 503 –25 . doi :10. 1016/ 0969-8051(93)90082-6 . PMID 83 89223.

Doorduin J, de Vries EF and Dierckx RA, et al. PET imaging of the peripheral benzodiazepine receptor: monitoring disease progression and therapy response in neurodegenerative disorders. Current Pharmaceutical Design. 2008; 14(31):3297–315. doi: 10. 2174 / 13 81 61208 786549443 . PMID 19075709.

Fiorenza D, Nicolai E and Cavaliere C, et al. Fully Automated Synthesis of Novel TSPO PETImaging Ligand [18F] Fluoroethyltemazepam. Molecules 2021; 26(2372):1-12.https:// doi.org /10.3390 /molecules26082372.

Guillon J, Boulouard M and Lelong V, et al. synthesis and preliminary behavioural evaluation in mice of new 3-aryl-3-pyrrol-1-ylpropanamides, analogues of FGIN-1-27 and FGIN-1-43, The Journal of Pharmacy and Pharmacology. 2001; 53 (11): 1561–8. doi: 10.1211/0022 3570 117779 45 . PMID 11732760.

Novitskii AA, Bochkov PO and Shevchenko RV, et al. Metabolism of a Novel Anxiolytic GML-1 in Rats. Bull Exp Biol Med. 2018; 165(6):751-3. doi: 10.1007/s10517-018-4257-9.

Grimm A, Lejri I and Hallé F, et al. Mitochondria modulatory effects of new TSPO ligands in a cellular model of tauopathies, J Neuroendocrinol. 2020; 32(1):e12796. doi: 10.1111/jne.12796.

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2024-03-26