Display options
Cite
Nieto A, Bailey T, Kaczanowska K, et al. GABA. Curr Top Behav Neurosci. 2022;52:81-118doi: 10.1007/7854_2021_232.
Nieto, A., Bailey, T., Kaczanowska, K., & McDonald, P. (2022). GABA. Current topics in behavioral neurosciences, 5281-118. https://doi.org/10.1007/7854_2021_232
Nieto, A, et al. "GABA." Current topics in behavioral neurosciences vol. 52 (2022): 81-118. doi: https://doi.org/10.1007/7854_2021_232
Nieto A, Bailey T, Kaczanowska K, McDonald P. GABA. Curr Top Behav Neurosci. 2022;52:81-118. doi: 10.1007/7854_2021_232. PMID: 34036555.
Copy Download .nbib Format: NLM
Share it on

Curr Top Behav Neurosci. 2022;52:81-118. doi: 10.1007/7854_2021_232.

GABA.

Current topics in behavioral neurosciences

A Nieto, T Bailey, K Kaczanowska, P McDonald

Affiliations

  1. Department of Cancer Physiology, Moffitt Cancer Center, Tampa, FL, USA.
  2. Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
  3. Department of Cancer Physiology, Moffitt Cancer Center, Tampa, FL, USA. [email protected].

PMID: 34036555 DOI: 10.1007/7854_2021_232

Abstract

The GABA

© 2021. Springer Nature Switzerland AG.

Keywords: GABAB receptor pharmacology; Orthosteric and allosteric modulators; Therapeutic target

References

  1. Agabio R, Colombo G (2014) GABAB receptor ligands for the treatment of alcohol use disorder: preclinical and clinical evidence. Front Neurosci 8:140 - PubMed
  2. Agabio R, Colombo G (2015) GABAB receptor as therapeutic target for drug addiction: from baclofen to positive allosteric modulators. Psychiatr Pol 49(2):215–223 - PubMed
  3. Agabio R, Sinclair JM, Addolorato G, Aubin HJ, Beraha EM, Caputo F, Chick JD, de La Selle P, Franchitto N, Garbutt JC, Haber PS, Heydtmann M, Jaury P, Lingford-Hughes AR, Morley KC, Müller CA, Owens L, Pastor A, Paterson LM, Pélissier F, Rolland B, Stafford A, Thompson A, van den Brink W, de Beaurepaire R, Leggio L (2018) Baclofen for the treatment of alcohol use disorder: the Cagliari statement. Lancet Psychiatry 5(12):957–960 - PubMed
  4. Al-Wadei HA, Al-Wadei MH, Ullah MF, Schuller HM (2012) Celecoxib and GABA cooperatively prevent the progression of pancreatic cancer in vitro and in xenograft models of stress-free and stress-exposed mice. PLoS One 7(8):e43376 - PubMed
  5. Awapara J (1950) Occurrence of free gamma-aminobutyric acid in brain and its formation from L-glutamic acid. Tex Rep Biol Med 8(4):443–447 - PubMed
  6. Balasubramanian S, Fam SR, Hall RA (2007) GABAB receptor association with the PDZ scaffold Mupp1 alters receptor stability and function. J Biol Chem 282(6):4162–4171 - PubMed
  7. Bartoi T, Rigbolt KT, Du D, Köhr G, Blagoev B, Kornau HC (2010) GABAB receptor constituents revealed by tandem affinity purification from transgenic mice. J Biol Chem 285(27):20625–20633 - PubMed
  8. Basmajian JV (1975) Lioresal (baclofen) treatment of spasticity in multiple sclerosis. Am J Phys Med 54(4):175–177 - PubMed
  9. Bauer U, Brailsford W, Chhajlani V, Egner B, Fjellström O, Gustafsson L, Mattsson J, Nilsson K, Olsson T (2005) Imidazole variants as modulators of gaba receptor for the treatment of GI disorders. U.S. Patent 20080269216 - PubMed
  10. Benarroch EE (2012) GABAB receptors: structure, functions, and clinical implications. Neurology 78(8):578–584 - PubMed
  11. Benke D (2013) GABAB receptor trafficking and interacting proteins: targets for the development of highly specific therapeutic strategies to treat neurological disorders? Biochem Pharmacol 86(11):1525–1530 - PubMed
  12. Berg KA, Clarke WP (2018) Making sense of pharmacology: inverse agonism and functional selectivity. Int J Neuropsychopharmacol 21(10):962–977 - PubMed
  13. Bernasconi R, Lauber J, Marescaux C, Vergnes M, Martin P, Rubio V, Leonhardt T, Reymann N, Bittiger H (1992) Experimental absence seizures: potential role of gamma-hydroxybutyric acid and GABAB receptors. J Neural Transm Suppl 35:155–177 - PubMed
  14. Berry-Kravis E, Hagerman R, Visootsak J, Budimirovic D, Kaufmann WE, Cherubini M, Zarevics P, Walton-Bowen K, Wang P, Bear MF, Carpenter RL (2017) Arbaclofen in fragile X syndrome: results of phase 3 trials. J Neurodev Disord 9:3 - PubMed
  15. Bertrand S, Ng GY, Purisai MG, Wolfe SE, Severidt MW, Nouel D, Robitaille R, Low MJ, O’Neill GP, Metters K, Lacaille JC, Chronwall BM, Morris SJ (2001) The anticonvulsant, antihyperalgesic agent gabapentin is an agonist at brain gamma-aminobutyric acid type B receptors negatively coupled to voltage-dependent calcium channels. J Pharmacol Exp Ther 298(1):15–24 - PubMed
  16. Bettler B, Tiao JY (2006) Molecular diversity, trafficking and subcellular localization of GABAB receptors. Pharmacol Ther 110(3):533–543 - PubMed
  17. Bettler B, Kaupmann K, Mosbacher J, Gassmann M (2004) Molecular structure and physiological functions of GABA(B) receptors. Physiol Rev 84(3):835–867 - PubMed
  18. Bianchi M, Panerai AE (1993) Reversal of scopolamine-induced amnesia by the GABAB receptor antagonist CGP 35348 in the mouse. Brain Res Cogn Brain Res 1(2):135–136 - PubMed
  19. Billinton A, Baird VH, Thom M, Duncan JS, Upton N, Bowery NG (2001a) GABA(B) receptor autoradiography in hippocampal sclerosis associated with human temporal lobe epilepsy. Br J Pharmacol 132(2):475–480 - PubMed
  20. Billinton A, Ige AO, Bolam JP, White JH, Marshall FH, Emson PC (2001b) Advances in the molecular understanding of GABA(B) receptors. Trends Neurosci 24(5):277–282 - PubMed
  21. Binet V, Brajon C, Le Corre L, Acher F, Pin JP, Prezeau L (2004) The heptahelical domain of GABA(B2) is activated directly by CGP7930, a positive allosteric modulator of the GABA(B) receptor. J Biol Chem 279(28):29085–29091 - PubMed
  22. Black SW, Morairty SR, Chen TM, Leung AK, Wisor JP, Yamanaka A, Kilduff TS (2014) GABAB agonism promotes sleep and reduces cataplexy in murine narcolepsy. J Neurosci 34(19):6485–6494 - PubMed
  23. Blein S, Ginham R, Uhrin D, Smith BO, Soares DC, Veltel S, McIlhinney RA, White JH, Barlow PN (2004) Structural analysis of the complement control protein (CCP) modules of GABA(B) receptor 1a: only one of the two CCP modules is compactly folded. J Biol Chem 279(46):48292–48306 - PubMed
  24. Bolser DC, Blythin DJ, Chapman RW, Egan RW, Hey JA, Rizzo C, Kuo SC, Kreutner W (1995) The pharmacology of SCH 50911: a novel, orally-active GABA-beta receptor antagonist. J Pharmacol Exp Ther 274(3):1393–1398 - PubMed
  25. Bon C, Galvan M (1996) Electrophysiological actions of GABAB agonists and antagonists in rat dorso-lateral septal neurones in vitro. Br J Pharmacol 118(4):961–967 - PubMed
  26. Bonaventura MM, Catalano PN, Chamson-Reig A, Arany E, Hill D, Bettler B, Saravia F, Libertun C, Lux-Lantos VA (2008) GABAB receptors and glucose homeostasis: evaluation in GABAB receptor knockout mice. Am J Physiol Endocrinol Metab 294(1):E157–E167 - PubMed
  27. Bonaventura MM, Crivello M, Ferreira ML, Repetto M, Cymeryng C, Libertun C, Lux-Lantos VA (2012) Effects of GABAB receptor agonists and antagonists on glycemia regulation in mice. Eur J Pharmacol 677(1–3):188–196 - PubMed
  28. Borza I, Román V, Éles J, Hadady Z, Huszár J (2018) Pharmacologically active aryl-substituted pyrazolo[1,5-a]pyrimidine derivatives. W.O. Patent 2018167629 - PubMed
  29. Bowery NG (1993) GABAB receptor pharmacology. Annu Rev Pharmacol Toxicol 33:109–147 - PubMed
  30. Bowery NG, Doble A, Hill DR, Hudson AL, Shaw JS, Turnbull MJ (1979) Baclofen: a selective agonist for a novel type of GABA receptor proceedings. Br J Pharmacol 67(3):444p–445p - PubMed
  31. Bowery NG, Hill DR, Hudson AL, Doble A, Middlemiss DN, Shaw J, Turnbull M (1980) (−)Baclofen decreases neurotransmitter release in the mammalian CNS by an action at a novel GABA receptor. Nature 283(5742):92–94 - PubMed
  32. Bowery NG, Doble A, Hill DR, Hudson AL, Shaw JS, Turnbull MJ, Warrington R (1981) Bicuculline-insensitive GABA receptors on peripheral autonomic nerve terminals. Eur J Pharmacol 71(1):53–70 - PubMed
  33. Bowery NG, Bettler B, Froestl W, Gallagher JP, Marshall F, Raiteri M, Bonner TI, Enna SJ (2002) International Union of Pharmacology. XXXIII. Mammalian gamma-aminobutyric acid(B) receptors: structure and function. Pharmacol Rev 54(2):247–264 - PubMed
  34. Bowery N, Enna SJ, Olsen RW (2004) Six decades of GABA. Biochem Pharmacol 68(8):1477–1478 - PubMed
  35. Braun M, Wendt A, Buschard K, Salehi A, Sewing S, Gromada J, Rorsman P (2004) GABAB receptor activation inhibits exocytosis in rat pancreatic beta-cells by G-protein-dependent activation of calcineurin. J Physiol 559(Pt 2):397–409 - PubMed
  36. Bredenoord AJ (2009) Lesogaberan, a GABA(B) agonist for the potential treatment of gastroesophageal reflux disease. IDrugs 12(9):576–584 - PubMed
  37. Broft AI, Spanos A, Corwin RL, Mayer L, Steinglass J, Devlin MJ, Attia E, Walsh BT (2007) Baclofen for binge eating: an open-label trial. Int J Eat Disord 40(8):687–691 - PubMed
  38. Bullock R (2005) SGS-742 Novartis. Curr Opin Investig Drugs 6(1):108–113 - PubMed
  39. Burford NT, Clark MJ, Wehrman TS, Gerritz SW, Banks M, O’Connell J, Traynor JR, Alt A (2013) Discovery of positive allosteric modulators and silent allosteric modulators of the μ-opioid receptor. Proc Natl Acad Sci U S A 110(26):10830–10835 - PubMed
  40. Busardò FP, Jones AW (2015) GHB pharmacology and toxicology: acute intoxication, concentrations in blood and urine in forensic cases and treatment of the withdrawal syndrome. Curr Neuropharmacol 13(1):47–70 - PubMed
  41. Calebiro D, Rieken F, Wagner J, Sungkaworn T, Zabel U, Borzi A, Cocucci E, Zürn A, Lohse MJ (2013) Single-molecule analysis of fluorescently labeled G-protein-coupled receptors reveals complexes with distinct dynamics and organization. Proc Natl Acad Sci U S A 110(2):743–748 - PubMed
  42. Cao W, Zhang R (2020) Research advance of underlying pathogenesis and target therapies in Charcot-Marie-tooth disease type 1A. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 37(5):578–583 - PubMed
  43. Castelli MP, Casu A, Casti P, Lobina C, Carai MA, Colombo G, Solinas M, Giunta D, Mugnaini C, Pasquini S, Tafi A, Brogi S, Gessa GL, Corelli F (2012) Characterization of COR627 and COR628, two novel positive allosteric modulators of the GABA(B) receptor. J Pharmacol Exp Ther 340(3):529–538 - PubMed
  44. Chapman RW, Danko G, del Prado M, Egan RW, Kreutner W, Rizzo CA, Hey JA (1993) Further evidence for prejunctional GABA-B inhibition of cholinergic and peptidergic bronchoconstriction in guinea pigs: studies with new agonists and antagonists. Pharmacology 46(6):315–323 - PubMed
  45. CHEMBL (n.d.) Database Release 27. https://www.ebi.ac.uk/chembl/ - PubMed
  46. Chen LH, Sun B, Zhang Y, Xu TJ, Xia ZX, Liu JF, Nan FJ (2014) Discovery of a negative allosteric modulator of GABAB receptors. ACS Med Chem Lett 5(7):742–747 - PubMed
  47. Cheng L, Karle M (2008) Quinoline compounds having an activity against the gabab receptor. W.O. Patent 2009041904A1 - PubMed
  48. Cheng L, Holmqvist S, Raubacher F, Schell P (2008a) Xanthine compounds having a positive allosteric gabab receptor modulator effect. W.O. Patent 2008130314A1 - PubMed
  49. Cheng L, Jonforsen M, Schell P (2008b) Pteridine compounds having activity on the gaba-receptors. W.O. Patent 2009041905 - PubMed
  50. Chung KF (2015) NMDA and GABA receptors as potential targets in cough hypersensitivity syndrome. Curr Opin Pharmacol 22:29–36 - PubMed
  51. Clarke JO, Fernandez-Becker NQ, Regalia KA, Triadafilopoulos G (2018) Baclofen and gastroesophageal reflux disease: seeing the forest through the trees. Clin Transl Gastroenterol 9(3):137–137 - PubMed
  52. Coffey JR, Cahill D, Steers W, Park TS, Ordia J, Meythaler J, Herman R, Shetter AG, Levy R, Gill B et al (1993) Intrathecal baclofen for intractable spasticity of spinal origin: results of a long-term multicenter study. J Neurosurg 78(2):226–232 - PubMed
  53. Comps-Agrar L, Kniazeff J, Nørskov-Lauritsen L, Maurel D, Gassmann M, Gregor N, Prézeau L, Bettler B, Durroux T, Trinquet E, Pin JP (2011) The oligomeric state sets GABA(B) receptor signalling efficacy. EMBO J 30(12):2336–2349 - PubMed
  54. Comps-Agrar L, Kniazeff J, Brock C, Trinquet E, Pin JP (2012) Stability of GABAB receptor oligomers revealed by dual TR-FRET and drug-induced cell surface targeting. FASEB J 26(8):3430–3439 - PubMed
  55. Cortez MA, Wu Y, Gibson KM, Snead OC 3rd (2004) Absence seizures in succinic semialdehyde dehydrogenase deficient mice: a model of juvenile absence epilepsy. Pharmacol Biochem Behav 79(3):547–553 - PubMed
  56. Costantino G, Macchiarulo A, Entrena Guadix A, Pellicciari R (2001) QSAR and molecular modeling studies of baclofen analogues as GABA(B) agonists. Insights into the role of the aromatic moiety in GABA(B) binding and activation. J Med Chem 44(11):1827–1832 - PubMed
  57. Couve A, Filippov AK, Connolly CN, Bettler B, Brown DA, Moss SJ (1998) Intracellular retention of recombinant GABAB receptors. J Biol Chem 273(41):26361–26367 - PubMed
  58. Couve A, Kittler JT, Uren JM, Calver AR, Pangalos MN, Walsh FS, Moss SJ (2001) Association of GABA(B) receptors and members of the 14-3-3 family of signaling proteins. Mol Cell Neurosci 17(2):317–328 - PubMed
  59. Cryan JF, Kaupmann K (2005) Don’t worry ‘B’ happy!: a role for GABA(B) receptors in anxiety and depression. Trends Pharmacol Sci 26(1):36–43 - PubMed
  60. Cryan JF, Slattery DA (2010) GABAB receptors and depression: current status. Adv Pharmacol 58:427–451 - PubMed
  61. Curtis DR, Duggan AW, Felix D, Johnston GA (1970) GABA, bicuculline and central inhibition. Nature 226(5252):1222–1224 - PubMed
  62. de Miguel E, Vekovischeva O, Kuokkanen K, Vesajoki M, Paasikoski N, Kaskinoro J, Myllymaki M, Lainiola M, Janhunen SK, Hyytia P, Linden AM, Korpi ER (2019) GABAB receptor positive allosteric modulators with different efficacies affect neuroadaptation to and self-administration of alcohol and cocaine. Addict Biol 24(6):1191–1203 - PubMed
  63. Didiášová M, Banning A, Brennenstuhl H, Jung-Klawitter S, Cinquemani C, Opladen T, Tikkanen R (2020) Succinic semialdehyde dehydrogenase deficiency: an update. Cell 9(2):477 - PubMed
  64. Dinamarca MC, Raveh A, Schneider A, Fritzius T, Früh S, Rem PD, Stawarski M, Lalanne T, Turecek R, Choo M, Besseyrias V, Bildl W, Bentrop D, Staufenbiel M, Gassmann M, Fakler B, Schwenk J, Bettler B (2019) Complex formation of APP with GABA(B) receptors links axonal trafficking to amyloidogenic processing. Nat Commun 10(1):1331 - PubMed
  65. Drake RG, Davis LL, Cates ME, Jewell ME, Ambrose SM, Lowe JS (2003) Baclofen treatment for chronic posttraumatic stress disorder. Ann Pharmacother 37(9):1177–1181 - PubMed
  66. Dreifuss JJ, Kelly JS, Krnjević K (1969) Cortical inhibition and gamma-aminobutyric acid. Exp Brain Res 9(2):137–154 - PubMed
  67. Dupuis DS, Relkovic D, Lhuillier L, Mosbacher J, Kaupmann K (2006) Point mutations in the transmembrane region of GABAB2 facilitate activation by the positive modulator N,N′-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine (GS39783) in the absence of the GABAB1 subunit. Mol Pharmacol 70(6):2027–2036 - PubMed
  68. Dutar P, Nicoll RA (1988) A physiological role for GABAB receptors in the central nervous system. Nature 332(6160):156–158 - PubMed
  69. Duthey B, Caudron S, Perroy J, Bettler B, Fagni L, Pin JP, Prézeau L (2002) A single subunit (GB2) is required for G-protein activation by the heterodimeric GABA(B) receptor. J Biol Chem 277(5):3236–3241 - PubMed
  70. Dyer T (2013) Addex announces positive data with ADX71441 in a pre-clinical transgenic model of charcot-marie-tooth 1A disease. Addex Therapeutics, Geneva - PubMed
  71. Enna SJ, McCarson KE (2006) The role of GABA in the mediation and perception of pain. Adv Pharmacol 54:1–27 - PubMed
  72. Evenseth LM, Warszycki D, Bojarski AJ, Gabrielsen M, Sylte I (2019) In silico methods for the discovery of orthosteric GABAB receptor compounds. Molecules 24(5):935 - PubMed
  73. Faghih R, Moeller A, Ochse M, Pohlki F, Schmidt M, Sippy K, Turner S, van der Kam EL (2016) Substituted pyrazolopyrimidines and method of use. U.S. Patent 9828381B2 - PubMed
  74. Felice D, O’Leary OF, Pizzo RC, Cryan JF (2012) Blockade of the GABA(B) receptor increases neurogenesis in the ventral but not dorsal adult hippocampus: relevance to antidepressant action. Neuropharmacology 63(8):1380–1388 - PubMed
  75. Floersheim P, Froestl W, Guery S, Kaupmann K, Koller M (2006) Pyrimidine derivatives for the treatment of Gaba B mediated nervous system disorders. U.S Pantent 20100179127A1 - PubMed
  76. Francisco GE, Kothari S, Huls C (2001) GABA agonists and gabapentin for spastic hypertonia. Phys Med Rehabil Clin N Am 12(4):875–888, viii - PubMed
  77. Frankowska M, Filip M, Przegalinski E (2007) Effects of GABAB receptor ligands in animal tests of depression and anxiety. Pharmacol Rep 59(6):645–655 - PubMed
  78. Fritzius T, Bettler B (2020) The organizing principle of GABA(B) receptor complexes: physiological and pharmacological implications. Basic Clin Pharmacol Toxicol 126(Suppl 6):25–34 - PubMed
  79. Froestl W (2010) Chemistry and pharmacology of GABAB receptor ligands. In: GABAB receptor pharmacology – a tribute to Norman Bowery, pp 19–62 - PubMed
  80. Froestl W, Mickel SJ, Hall RG, von Sprecher G, Strub D, Baumann PA, Brugger F, Gentsch C, Jaekel J, Olpe HR et al (1995a) Phosphinic acid analogues of GABA. 1. New potent and selective GABAB agonists. J Med Chem 38(17):3297–3312 - PubMed
  81. Froestl W, Mickel SJ, von Sprecher G, Diel PJ, Hall RG, Maier L, Strub D, Melillo V, Baumann PA, Bernasconi R et al (1995b) Phosphinic acid analogues of GABA. 2. Selective, orally active GABAB antagonists. J Med Chem 38(17):3313–3331 - PubMed
  82. Froestl W, Gallagher M, Jenkins H, Madrid A, Melcher T, Teichman S, Mondadori CG, Pearlman R (2004) SGS742: the first GABA(B) receptor antagonist in clinical trials. Biochem Pharmacol 68(8):1479–1487 - PubMed
  83. Frye RE (2014) Clinical potential, safety, and tolerability of arbaclofen in the treatment of autism spectrum disorder. Drug Healthc Patient Saf 6:69–76 - PubMed
  84. Galvez T, Parmentier ML, Joly C, Malitschek B, Kaupmann K, Kuhn R, Bittiger H, Froestl W, Bettler B, Pin JP (1999) Mutagenesis and modeling of the GABAB receptor extracellular domain support a venus flytrap mechanism for ligand binding. J Biol Chem 274(19):13362–13369 - PubMed
  85. Galvez T, Prezeau L, Milioti G, Franek M, Joly C, Froestl W, Bettler B, Bertrand HO, Blahos J, Pin JP (2000) Mapping the agonist-binding site of GABAB type 1 subunit sheds light on the activation process of GABAB receptors. J Biol Chem 275(52):41166–41174 - PubMed
  86. Galvez T, Duthey B, Kniazeff J, Blahos J, Rovelli G, Bettler B, Prézeau L, Pin JP (2001) Allosteric interactions between GB1 and GB2 subunits are required for optimal GABA(B) receptor function. EMBO J 20(9):2152–2159 - PubMed
  87. Gemignani A, Paudice P, Bonanno G, Raiteri M (1994) Pharmacological discrimination between gamma-aminobutyric acid type B receptors regulating cholecystokinin and somatostatin release from rat neocortex synaptosomes. Mol Pharmacol 46(3):558–562 - PubMed
  88. Geng Y, Bush M, Mosyak L, Wang F, Fan QR (2013) Structural mechanism of ligand activation in human GABA(B) receptor. Nature 504(7479):254–259 - PubMed
  89. Getova DP, Dimitrova DD (2007) Effects of GABAB receptor antagonists CGP63360, CGP76290A and CGP76291A on learning and memory processes in rodents. Cent Eur J Med 2:280–293 - PubMed
  90. Gjoni T, Urwyler S (2009) Changes in the properties of allosteric and orthosteric GABAB receptor ligands after a continuous, desensitizing agonist pretreatment. Eur J Pharmacol 603(1–3):37–41 - PubMed
  91. Glausier JR, Lewis DA (2017) GABA and schizophrenia: where we stand and where we need to go. Schizophr Res 181:2–3 - PubMed
  92. Grunewald S, Schupp BJ, Ikeda SR, Kuner R, Steigerwald F, Kornau HC, Kohr G (2002) Importance of the gamma-aminobutyric acid(B) receptor C-termini for G-protein coupling. Mol Pharmacol 61(5):1070–1080 - PubMed
  93. Han C, Salyer AE, Kim EH, Jiang X, Jarrard RE, Powers MS, Kirchhoff AM, Salvador TK, Chester JA, Hockerman GH, Colby DA (2013) Evaluation of difluoromethyl ketones as agonists of the γ-aminobutyric acid type B (GABAB) receptor. J Med Chem 56(6):2456–2465 - PubMed
  94. Hannan S, Wilkins ME, Smart TG (2012) Sushi domains confer distinct trafficking profiles on GABAB receptors. Proc Natl Acad Sci U S A 109(30):12171–12176 - PubMed
  95. Hawrot E, Xiao Y, Shi QL, Norman D, Kirkitadze M, Barlow PN (1998) Demonstration of a tandem pair of complement protein modules in GABA(B) receptor 1a. FEBS Lett 432(3):103–108 - PubMed
  96. Helm KA, Haberman RP, Dean SL, Hoyt EC, Melcher T, Lund PK, Gallagher M (2005) GABAB receptor antagonist SGS742 improves spatial memory and reduces protein binding to the cAMP response element (CRE) in the hippocampus. Neuropharmacology 48(7):956–964 - PubMed
  97. Hinton T, Chebib M, Johnston GA (2008) Enantioselective actions of 4-amino-3-hydroxybutanoic acid and (3-amino-2-hydroxypropyl)methylphosphinic acid at recombinant GABA(C) receptors. Bioorg Med Chem Lett 18(1):402–404 - PubMed
  98. Hirst WD, Babbs AJ, Green A, Minton JA, Shaw TE, Wise A, Rice SQ, Pangalos MN, Price GW (2003) Pharmacological characterisation of a cell line expressing GABA B1b and GABA B2 receptor subunits. Biochem Pharmacol 65(7):1103–1113 - PubMed
  99. Hudgson P, Weightman D (1971) Baclofen in the treatment of spasticity. Br Med J 4(5778):15–17 - PubMed
  100. Jacobson LH, Vlachou S, Slattery DA, Li X, Cryan JF (2018) The gamma-aminobutyric acid b receptor in depression and reward. Biol Psychiatry 83(11):963–976 - PubMed
  101. Jensen AA, Mosbacher J, Elg S, Lingenhoehl K, Lohmann T, Johansen TN, Abrahamsen B, Mattsson JP, Lehmann A, Bettler B, Bräuner-Osborne H (2002) The anticonvulsant gabapentin (neurontin) does not act through gamma-aminobutyric acid-B receptors. Mol Pharmacol 61(6):1377–1384 - PubMed
  102. Jiang X, Su L, Zhang Q, He C, Zhang Z, Yi P, Liu J (2012) GABAB receptor complex as a potential target for tumor therapy. J Histochem Cytochem 60(4):269–279 - PubMed
  103. Johnston GA (1986) Multiplicity of GABA receptors. In: Benzodiazepine/GABA receptors and chloride channels. Receptor biochemistry and methodology. A.R. Liss - PubMed
  104. Jones KA, Borowsky B, Tamm JA, Craig DA, Durkin MM, Dai M, Yao WJ, Johnson M, Gunwaldsen C, Huang LY, Tang C, Shen Q, Salon JA, Morse K, Laz T, Smith KE, Nagarathnam D, Noble SA, Branchek TA, Gerald C (1998) GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2. Nature 396(6712):674–679 - PubMed
  105. Jouney EA (2019) Phenibut (β-phenyl-γ-aminobutyric acid): an easily obtainable “dietary supplement” with propensities for physical dependence and addiction. Curr Psychiatry Rep 21(4):23 - PubMed
  106. Kalinichev M, Girard F, Haddouk H, Rouillier M, Riguet E, Royer-Urios I, Mutel V, Lütjens R, Poli S (2017) The drug candidate, ADX71441, is a novel, potent and selective positive allosteric modulator of the GABA(B) receptor with a potential for treatment of anxiety, pain and spasticity. Neuropharmacology 114:34–47 - PubMed
  107. Kaupmann K, Huggel K, Heid J, Flor PJ, Bischoff S, Mickel SJ, McMaster G, Angst C, Bittiger H, Froestl W, Bettler B (1997) Expression cloning of GABA(B) receptors uncovers similarity to metabotropic glutamate receptors. Nature 386(6622):239–246 - PubMed
  108. Kaupmann K, Malitschek B, Schuler V, Heid J, Froestl W, Beck P, Mosbacher J, Bischoff S, Kulik A, Shigemoto R, Karschin A, Bettler B (1998) GABA(B)-receptor subtypes assemble into functional heteromeric complexes. Nature 396(6712):683–687 - PubMed
  109. Keating GM (2014) Sodium oxybate: a review of its use in alcohol withdrawal syndrome and in the maintenance of abstinence in alcohol dependence. Clin Drug Investig 34(1):63–80 - PubMed
  110. Keberle H, Faigle JW, Wilhelm M (1964) Gamma-amino-beta-(para-halophenyl)-butyric acids and their esters. U.S. Patent 3471548A - PubMed
  111. Keberle H, Faigle JW, Wilhelm M (1969) Gamma-amino-beta-(para-halophenyl)-butyric acids and their esters. Google Patents - PubMed
  112. Kenakin T (2004) Efficacy as a vector: the relative prevalence and paucity of inverse agonism. Mol Pharmacol 65(1):2–11 - PubMed
  113. Kenakin T (2005) New concepts in drug discovery: collateral efficacy and permissive antagonism. Nat Rev Drug Discov 4(11):919–927 - PubMed
  114. Kenakin T (2017) Signaling bias in drug discovery. Expert Opin Drug Discovery 12(4):321–333 - PubMed
  115. Kenakin T, Miller LJ (2010) Seven transmembrane receptors as shapeshifting proteins: the impact of allosteric modulation and functional selectivity on new drug discovery. Pharmacol Rev 62(2):265–304 - PubMed
  116. Kent CN, Park C, Lindsley CW (2020) Classics in chemical neuroscience: baclofen. ACS Chem Neurosci 11(12):1740–1755 - PubMed
  117. Keov P, Sexton PM, Christopoulos A (2011) Allosteric modulation of G protein-coupled receptors: a pharmacological perspective. Neuropharmacology 60(1):24–35 - PubMed
  118. Kerr DI, Ong J, Prager RH, Gynther BD, Curtis DR (1987) Phaclofen: a peripheral and central baclofen antagonist. Brain Res 405(1):150–154 - PubMed
  119. Kerr DI, Ong J, Johnston GA, Abbenante J, Prager RH (1988) 2-Hydroxy-saclofen: an improved antagonist at central and peripheral GABAB receptors. Neurosci Lett 92(1):92–96 - PubMed
  120. Kerr DI, Ong J, Puspawati NM, Prager RH (2002) Arylalkylamines are a novel class of positive allosteric modulators at GABA(B) receptors in rat neocortex. Eur J Pharmacol 451(1):69–77 - PubMed
  121. Kerr DIB, Khalafy J, Ong J, Perkins MV, Prager RH, Puspawati NM, Rimaz M (2006) Synthesis and biological activity of allosteric modulators of GABAB receptors, part 2. 3-(2,6-Bis-tert-butyl-4-hydroxyphenyl)propanols. Aust J Chem 59(7):457–462 - PubMed
  122. Kim W, Seo H (2014) Baclofen, a GABAB receptor agonist, enhances ubiquitin-proteasome system functioning and neuronal survival in Huntington’s disease model mice. Biochem Biophys Res Commun 443(2):706–711 - PubMed
  123. Kleppner SR, Tobin AJ (2001) GABA signalling: therapeutic targets for epilepsy, Parkinson’s disease and Huntington’s disease. Emerg Thera Targets 5(2):219–239 - PubMed
  124. Kniazeff J, Galvez T, Labesse G, Pin JP (2002) No ligand binding in the GB2 subunit of the GABA(B) receptor is required for activation and allosteric interaction between the subunits. J Neurosci 22(17):7352–7361 - PubMed
  125. Koek W, Cheng K, Rice KC (2013) Discriminative stimulus effects of the GABAB receptor-positive modulator rac-BHFF: comparison with GABAB receptor agonists and drugs of abuse. J Pharmacol Exp Ther 344(3):553–560 - PubMed
  126. Korsgaard S (1976) Baclofen (Lioresal) in the treatment ofneuroleptic-induced tardive dyskinesia. Acta Psychiatr Scand 54(1):17–24 - PubMed
  127. Krnjević K, Schwartz S (1966) Is gamma-aminobutyric acid an inhibitory transmitter? Nature 211(5056):1372–1374 - PubMed
  128. Lanneau C, Green A, Hirst WD, Wise A, Brown JT, Donnier E, Charles KJ, Wood M, Davies CH, Pangalos MN (2001) Gabapentin is not a GABAB receptor agonist. Neuropharmacology 41(8):965–975 - PubMed
  129. Lapin I (2001) Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug. CNS Drug Rev 7(4):471–481 - PubMed
  130. Lasarge CL, Banuelos C, Mayse JD, Bizon JL (2009) Blockade of GABA(B) receptors completely reverses age-related learning impairment. Neuroscience 164(3):941–947 - PubMed
  131. Lehmann A (2009) GABAB receptors as drug targets to treat gastroesophageal reflux disease. Pharmacol Ther 122(3):239–245 - PubMed
  132. Lehmann A, Jensen JM, Boeckxstaens GE (2010) GABAB receptor agonism as a novel therapeutic modality in the treatment of gastroesophageal reflux disease. Adv Pharmacol 58:287–313 - PubMed
  133. Li X, Kaczanowska K, Finn MG, Markou A, Risbrough VB (2015) The GABA(B) receptor positive modulator BHF177 attenuated anxiety, but not conditioned fear, in rats. Neuropharmacology 97:357–364 - PubMed
  134. Li X, Sturchler E, Kaczanowska K, Cameron M, Finn MG, Griffin P, McDonald P, Markou A (2017) KK-92A, a novel GABAB receptor positive allosteric modulator, attenuates nicotine self-administration and cue-induced nicotine seeking in rats. Psychopharmacology 234(9–10):1633–1644 - PubMed
  135. Lingenhoehl K, Brom R, Heid J, Beck P, Froestl W, Kaupmann K, Bettler B, Mosbacher J (1999) Gamma-hydroxybutyrate is a weak agonist at recombinant GABA(B) receptors. Neuropharmacology 38(11):1667–1673 - PubMed
  136. Maccioni P, Colombo G (2019) Potential of GABA(B) receptor positive allosteric modulators in the treatment of alcohol use disorder. CNS Drugs 33(2):107–123 - PubMed
  137. Maccioni P, Zaru A, Loi B, Lobina C, Carai MA, Gessa GL, Capra A, Mugnaini C, Pasquini S, Corelli F, Hyytia P, Lumeng L, Colombo G (2012) Comparison of the effect of the GABABeta receptor agonist, baclofen, and the positive allosteric modulator of the GABAB receptor, GS39783, on alcohol self-administration in 3 different lines of alcohol-preferring rats. Alcohol Clin Exp Res 36(10):1748–1766 - PubMed
  138. Maccioni P, Vargiolu D, Thomas AW, Malherbe P, Mugnaini C, Corelli F, Leite-Morris KA, Gessa GL, Colombo G (2015) Inhibition of alcohol self-administration by positive allosteric modulators of the GABAB receptor in rats: lack of tolerance and potentiation of baclofen. Psychopharmacology 232(10):1831–1841 - PubMed
  139. Malherbe P, Masciadri R, Norcross RD, Prinssen E (2006) 3-methanesulfonylquinolines as GABAB enhancers. U.S. Patent 7728142B2 - PubMed
  140. Malherbe P, Masciadri R, Norcross RD, Ratni H, Thomas AW (2007) Thieno-pyridine derivatives as gaba-b allosteric enhancers. E.P.O. Patent 1828199 - PubMed
  141. Malherbe P, Masciadri R, Norcross RD, Knoflach F, Kratzeisen C, Zenner MT, Kolb Y, Marcuz A, Huwyler J, Nakagawa T, Porter RH, Thomas AW, Wettstein JG, Sleight AJ, Spooren W, Prinssen EP (2008) Characterization of (R,S)-5,7-di-tert-butyl-3-hydroxy-3-trifluoromethyl-3H-benzofuran-2-one as a positive allosteric modulator of GABAB receptors. Br J Pharmacol 154(4):797–811 - PubMed
  142. Mao C, Shen C, Li C, Shen DD, Xu C, Zhang S, Zhou R, Shen Q, Chen LN, Jiang Z, Liu J, Zhang Y (2020) Cryo-EM structures of inactive and active GABA(B) receptor. Cell Res 30(7):564–573 - PubMed
  143. Marcoli M, Scarrone S, Maura G, Bonanno G, Raiteri M (2000) A subtype of the gamma-aminobutyric acid(B) receptor regulates cholinergic twitch response in the guinea pig ileum. J Pharmacol Exp Ther 293(1):42–47 - PubMed
  144. Mares P, Kubova H (2008) What is the role of neurotransmitter systems in cortical seizures? Physiol Res 57(Suppl 3):S111–S120 - PubMed
  145. Marescaux C, Vergnes M, Bernasconi R (1992) GABAB receptor antagonists: potential new anti-absence drugs. J Neural Transm Suppl 35:179–188 - PubMed
  146. Margeta-Mitrovic M, Jan YN, Jan LY (2001) Ligand-induced signal transduction within heterodimeric GABA(B) receptor. Proc Natl Acad Sci U S A 98(25):14643–14648 - PubMed
  147. Markou A, Hauger RL, Koob GF (1992) Desmethylimipramine attenuates cocaine withdrawal in rats. Psychopharmacology 109(3):305–314 - PubMed
  148. Markou A, Kosten TR, Koob GF (1998) Neurobiological similarities in depression and drug dependence: a self-medication hypothesis. Neuropsychopharmacology 18(3):135–174 - PubMed
  149. Marshall FH, White J, Main M, Green A, Wise A (1999) GABA(B) receptors function as heterodimers. Biochem Soc Trans 27(4):530–535 - PubMed
  150. Martvon L, Kotmanova Z, Dobrolubov B, Babalova L, Simera M, Veternik M, Pitts T, Jakus J, Poliacek I (2020) Modulation of cough reflex by Gaba-ergic inhibition in medullary raphé of the cat. Physiol Res 69(Suppl 1):S151–s161 - PubMed
  151. Mathivet P, Bernasconi R, De Barry J, Marescaux C, Bittiger H (1997) Binding characteristics of gamma-hydroxybutyric acid as a weak but selective GABAB receptor agonist. Eur J Pharmacol 321(1):67–75 - PubMed
  152. Maurel D, Comps-Agrar L, Brock C, Rives ML, Bourrier E, Ayoub MA, Bazin H, Tinel N, Durroux T, Prézeau L, Trinquet E, Pin JP (2008) Cell-surface protein-protein interaction analysis with time-resolved FRET and snap-tag technologies: application to GPCR oligomerization. Nat Methods 5(6):561–567 - PubMed
  153. May LT, Avlani VA, Sexton PM, Christopoulos A (2004) Allosteric modulation of G protein-coupled receptors. Curr Pharm Des 10(17):2003–2013 - PubMed
  154. Meier SD, Kafitz KW, Rose CR (2008) Developmental profile and mechanisms of GABA-induced calcium signaling in hippocampal astrocytes. Glia 56(10):1127–1137 - PubMed
  155. Mendez D, Gaulton A, Bento AP, Chambers J, De Veij M, Félix E, Magariños MP, Mosquera JF, Mutowo P, Nowotka M, Gordillo-Marañón M, Hunter F, Junco L, Mugumbate G, Rodriguez-Lopez M, Atkinson F, Bosc N, Radoux CJ, Segura-Cabrera A, Hersey A, Leach AR (2019) ChEMBL: towards direct deposition of bioassay data. Nucleic Acids Res 47(D1):D930–d940 - PubMed
  156. Modaberi S, Heysieattalab S, Shahbazi M, Naghdi N (2019) Combination effects of forced mild exercise and GABA(B) receptor agonist on spatial learning, memory, and motor activity in striatum lesion rats. J Mot Behav 51(4):438–450 - PubMed
  157. Mombereau C, Kaupmann K, Froestl W, Sansig G, van der Putten H, Cryan JF (2004) Genetic and pharmacological evidence of a role for GABA(B) receptors in the modulation of anxiety- and antidepressant-like behavior. Neuropsychopharmacology 29(6):1050–1062 - PubMed
  158. Mondadori C, Jaekel J, Preiswerk G (1993) CGP 36742: the first orally active GABAB blocker improves the cognitive performance of mice, rats, and rhesus monkeys. Behav Neural Biol 60(1):62–68 - PubMed
  159. Morishita R, Kato K, Asano T (1990) GABAB receptors couple to G proteins Go, Go* and Gi1 but not to Gi2. FEBS Lett 271(1–2):231–235 - PubMed
  160. Mugnaini C, Pedani V, Casu A, Lobina C, Casti A, Maccioni P, Porcu A, Giunta D, Lamponi S, Solinas M, Dragoni S, Valoti M, Colombo G, Castelli MP, Gessa GL, Corelli F (2013) Synthesis and pharmacological characterization of 2-(acylamino)thiophene derivatives as metabolically stable, orally effective, positive allosteric modulators of the GABAB receptor. J Med Chem 56(9):3620–3635 - PubMed
  161. Mukherjee RS, McBride EW, Beinborn M, Dunlap K, Kopin AS (2006) Point mutations in either subunit of the GABAB receptor confer constitutive activity to the heterodimer. Mol Pharmacol 70(4):1406–1413 - PubMed
  162. Murai N, Kondo Y, Akuzawa S, Mihara T, Shiraishi N, Kakimoto S, Matsumoto M (2019) A novel GABA(B) receptor positive allosteric modulator, ASP8062, exerts analgesic effects in a rat model of fibromyalgia. Eur J Pharmacol 865:172750 - PubMed
  163. Naffaa MM, Hung S, Chebib M, Johnston GAR, Hanrahan JR (2017) GABA-ρ receptors: distinctive functions and molecular pharmacology. Br J Pharmacol 174(13):1881–1894 - PubMed
  164. Nair PC, McKinnon RA, Miners JO, Bastiampillai T (2020) Binding of clozapine to the GABA(B) receptor: clinical and structural insights. Mol Psychiatry 25:1910–1919 - PubMed
  165. Nambu A (2012) GABA-B receptor: possible target for Parkinson’s disease therapy. Exp Neurol 233(1):121–122 - PubMed
  166. Nehring RB, Horikawa HP, El Far O, Kneussel M, Brandstätter JH, Stamm S, Wischmeyer E, Betz H, Karschin A (2000) The metabotropic GABAB receptor directly interacts with the activating transcription factor 4. J Biol Chem 275(45):35185–35191 - PubMed
  167. Nemeth EF, Steffey ME, Hammerland LG, Hung BCP, Van Wagenen BC, DelMar EG, Balandrin MF (1998) Calcimimetics with potent and selective activity on the parathyroid calcium receptor. Proc Natl Acad Sci 95(7):4040–4045 - PubMed
  168. Neto FL, Ferreira-Gomes J, Castro-Lopes JM (2006) Distribution of GABA receptors in the thalamus and their involvement in nociception. Adv Pharmacol 54:29–51 - PubMed
  169. New DC, An H, Ip NY, Wong YH (2006) GABAB heterodimeric receptors promote Ca2+ influx via store-operated channels in rat cortical neurons and transfected Chinese hamster ovary cells. Neuroscience 137(4):1347–1358 - PubMed
  170. Ng GY, Bertrand S, Sullivan R, Ethier N, Wang J, Yergey J, Belley M, Trimble L, Bateman K, Alder L, Smith A, McKernan R, Metters K, O’Neill GP, Lacaille JC, Hébert TE (2001) Gamma-aminobutyric acid type B receptors with specific heterodimer composition and postsynaptic actions in hippocampal neurons are targets of anticonvulsant gabapentin action. Mol Pharmacol 59(1):144–152 - PubMed
  171. Niazi M, Skrtic S, Ruth M, Holmberg AA (2011) Pharmacokinetic profile of lesogaberan (AZD3355) in healthy subjects: a novel GABA(B)-receptor agonist reflux inhibitor. Drugs R&D 11(1):77–83 - PubMed
  172. Nishikawa M, Hirouchi M, Kuriyama K (1997) Functional coupling of Gi subtype with GABAB receptor/adenylyl cyclase system: analysis using a reconstituted system with purified GTP-binding protein from bovine cerebral cortex. Neurochem Int 31(1):21–25 - PubMed
  173. Niswender CM, Conn PJ (2010) Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol 50:295–322 - PubMed
  174. Nowak G, Partyka A, Palucha A, Szewczyk B, Wieronska JM, Dybala M, Metz M, Librowski T, Froestl W, Papp M, Pilc A (2006) Antidepressant-like activity of CGP 36742 and CGP 51176, selective GABAB receptor antagonists, in rodents. Br J Pharmacol 149(5):581–590 - PubMed
  175. Ohtsuki S, Asaba H, Takanaga H, Deguchi T, Hosoya K, Otagiri M, Terasaki T (2002) Role of blood-brain barrier organic anion transporter 3 (OAT3) in the efflux of indoxyl sulfate, a uremic toxin: its involvement in neurotransmitter metabolite clearance from the brain. J Neurochem 83(1):57–66 - PubMed
  176. Olpe HR, Demiéville H, Baltzer V, Bencze WL, Koella WP, Wolf P, Haas HL (1978) The biological activity of d- and l-baclofen (Lioresal). Eur J Pharmacol 52(1):133–136 - PubMed
  177. Ong J, Kerr DI (1984) Evidence for a physiological role of GABA in the control of guinea-pig intestinal motility. Neurosci Lett 50(1–3):339–343 - PubMed
  178. Ong J, Parker DA, Marino V, Kerr DI, Puspawati NM, Prager RH (2005) 3-Chloro,4-methoxyfendiline is a potent GABA(B) receptor potentiator in rat neocortical slices. Eur J Pharmacol 507(1–3):35–42 - PubMed
  179. Ostojić ZS, Ilić TV, Vesković SM, Andjus PR (2013) GABAB receptors as a common target for hypothermia and spike and wave seizures: intersecting mechanisms of thermoregulation and absence epilepsy. Neuroscience 238:39–58 - PubMed
  180. Pagano A, Rovelli G, Mosbacher J, Lohmann T, Duthey B, Stauffer D, Ristig D, Schuler V, Meigel I, Lampert C, Stein T, Prezeau L, Blahos J, Pin J, Froestl W, Kuhn R, Heid J, Kaupmann K, Bettler B (2001) C-terminal interaction is essential for surface trafficking but not for heteromeric assembly of GABA(b) receptors. J Neurosci 21(4):1189–1202 - PubMed
  181. Patel S, Naeem S, Kesingland A, Froestl W, Capogna M, Urban L, Fox A (2001) The effects of GABA(B) agonists and gabapentin on mechanical hyperalgesia in models of neuropathic and inflammatory pain in the rat. Pain 90(3):217–226 - PubMed
  182. Perdona E, Costantini VJ, Tessari M, Martinelli P, Carignani C, Valerio E, Mok MH, Zonzini L, Visentini F, Gianotti M, Gordon L, Rocheville M, Corsi M, Capelli AM (2011) In vitro and in vivo characterization of the novel GABAB receptor positive allosteric modulator, 2-{1-[2-(4-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-7-yl]-2-piperidinyl}eth anol (CMPPE). Neuropharmacology 61(5–6):957–966 - PubMed
  183. Pérez-Garci E, Gassmann M, Bettler B, Larkum ME (2006) The GABAB1b isoform mediates long-lasting inhibition of dendritic Ca2+ spikes in layer 5 somatosensory pyramidal neurons. Neuron 50(4):603–616 - PubMed
  184. Pinard A, Seddik R, Bettler B (2010) GABAB receptors: physiological functions and mechanisms of diversity. Adv Pharmacol 58:231–255 - PubMed
  185. Pirard B, Carrupt PA, Testa B, Tsai RS, Berthelot P, Vaccher C, Debaert M, Durant F (1995) Structure-affinity relationships of baclofen and 3-heteroaromatic analogues. Bioorg Med Chem 3(11):1537–1545 - PubMed
  186. Polenzani L, Woodward RM, Miledi R (1991) Expression of mammalian gamma-aminobutyric acid receptors with distinct pharmacology in Xenopus oocytes. Proc Natl Acad Sci U S A 88(10):4318–4322 - PubMed
  187. Pontier SM, Lahaie N, Ginham R, St-Gelais F, Bonin H, Bell DJ, Flynn H, Trudeau LE, McIlhinney J, White JH, Bouvier M (2006) Coordinated action of NSF and PKC regulates GABAB receptor signaling efficacy. EMBO J 25(12):2698–2709 - PubMed
  188. Porcu A, Lobina C, Giunta D, Solinas M, Mugnaini C, Castelli MP (2016) In vitro and in vivo pharmacological characterization of SSD114, a novel GABAB positive allosteric modulator. Eur J Pharmacol 791:115–123 - PubMed
  189. Prusis P, Höglund L, Törmakangas O, Hietanen A, Arvela R, Vesalainen A, Heikkinen T (2015) Pharmacologically active quinazolinedione derivatives. W.O. Patent 2015169999-A1 - PubMed
  190. Ranson DC, Ayoub SS, Corcoran O, Casalotti SO (2020) Pharmacological targeting of the GABA(B) receptor alters Drosophila’s behavioural responses to alcohol. Addict Biol 25(2):e12725 - PubMed
  191. Rice HC, de Malmazet D, Schreurs A, Frere S, Van Molle I, Volkov AN, Creemers E, Vertkin I, Nys J, Ranaivoson FM, Comoletti D, Savas JN, Remaut H, Balschun D, Wierda KD, Slutsky I, Farrow K, De Strooper B, de Wit J (2019) Secreted amyloid-β precursor protein functions as a GABA(B)R1a ligand to modulate synaptic transmission. Science 363(6423):eaao4827 - PubMed
  192. Riguet E, Campo B, Gibelin A, Mhalla K (2007) Triazinedione derivatives as GABAB receptor modulators. U.S. Patent 8344138B2 - PubMed
  193. Ritter B, Zschüntsch J, Kvachnina E, Zhang W, Ponimaskin EG (2004) The GABA(B) receptor subunits R1 and R2 interact differentially with the activation transcription factor ATF4 in mouse brain during the postnatal development. Brain Res Dev Brain Res 149(1):73–77 - PubMed
  194. Robbins MJ, Calver AR, Filippov AK, Hirst WD, Russell RB, Wood MD, Nasir S, Couve A, Brown DA, Moss SJ, Pangalos MN (2001) GABA(B2) is essential for g-protein coupling of the GABA(B) receptor heterodimer. J Neurosci 21(20):8043–8052 - PubMed
  195. Roberts E, Frankel S (1950) Gamma-aminobutyric acid in brain: its formation from glutamic acid. J Biol Chem 187(1):55–63 - PubMed
  196. Sahraei H, Askaripour M, Esmaeilpour K, Shahsavari F, Rajabi S, Moradi-Kor N (2019) GABA(B) receptor activation ameliorates spatial memory impairments in stress-exposed rats. Neuropsychiatr Dis Treat 15:1497–1506 - PubMed
  197. Sauter K, Grampp T, Fritschy JM, Kaupmann K, Bettler B, Mohler H, Benke D (2005) Subtype-selective interaction with the transcription factor CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) regulates cell surface expression of GABA(B) receptors. J Biol Chem 280(39):33566–33572 - PubMed
  198. Schofield PR, Darlison MG, Fujita N, Burt DR, Stephenson FA, Rodriguez H, Rhee LM, Ramachandran J, Reale V, Glencorse TA et al (1987) Sequence and functional expression of the GABA A receptor shows a ligand-gated receptor super-family. Nature 328(6127):221–227 - PubMed
  199. Schuller HM (2018) Regulatory role of G protein-coupled receptors in pancreatic cancer development and progression. Curr Med Chem 25(22):2566–2575 - PubMed
  200. Schuller HM, Al-Wadei HA, Majidi M (2008) GABA B receptor is a novel drug target for pancreatic cancer. Cancer 112(4):767–778 - PubMed
  201. Schwenk J, Metz M, Zolles G, Turecek R, Fritzius T, Bildl W, Tarusawa E, Kulik A, Unger A, Ivankova K, Seddik R, Tiao JY, Rajalu M, Trojanova J, Rohde V, Gassmann M, Schulte U, Fakler B, Bettler B (2010) Native GABA(B) receptors are heteromultimers with a family of auxiliary subunits. Nature 465(7295):231–235 - PubMed
  202. Schwenk J, Pérez-Garci E, Schneider A, Kollewe A, Gauthier-Kemper A, Fritzius T, Raveh A, Dinamarca MC, Hanuschkin A, Bildl W, Klingauf J, Gassmann M, Schulte U, Bettler B, Fakler B (2016) Modular composition and dynamics of native GABAB receptors identified by high-resolution proteomics. Nat Neurosci 19(2):233–242 - PubMed
  203. Seabrook GR, Howson W, Lacey MG (1990) Electrophysiological characterization of potent agonists and antagonists at pre- and postsynaptic GABAB receptors on neurones in rat brain slices. Br J Pharmacol 101(4):949–957 - PubMed
  204. Shiraishi N, Hoshii H, Hamaguchi W, Honjo E, Takuwa T, Kondo Y, Goto T (2014) Sulfur-Containing Bicyclic Compound. W.O. Patent 2015056771 - PubMed
  205. Sigel E, Steinmann ME (2012) Structure, function, and modulation of GABA(A) receptors. J Biol Chem 287(48):40224–40231 - PubMed
  206. Smith JS, Lefkowitz RJ, Rajagopal S (2018) Biased signalling: from simple switches to allosteric microprocessors. Nat Rev Drug Discov 17(4):243–260 - PubMed
  207. Snead OC 3rd (1992) Evidence for GABAB-mediated mechanisms in experimental generalized absence seizures. Eur J Pharmacol 213(3):343–349 - PubMed
  208. Sowaileh MF, Salyer AE, Roy KK, John JP, Woods JR, Doerksen RJ, Hockerman GH, Colby DA (2018) Agonists of the γ-aminobutyric acid type B (GABA(B)) receptor derived from β-hydroxy and β-amino difluoromethyl ketones. Bioorg Med Chem Lett 28(16):2697–2700 - PubMed
  209. Spangler S, Bruchas MR (2017) Tuning biased GPCR signaling for physiological gain. Cell 171(5):989–991 - PubMed
  210. Stewart LS, Wu Y, Eubanks JH, Han H, Leschenko Y, Perez Velazquez JL, Cortez MA, Snead OC 3rd (2009) Severity of atypical absence phenotype in GABAB transgenic mice is subunit specific. Epilepsy Behav 14(4):577–581 - PubMed
  211. Stewart GD, Comps-Agrar L, Nørskov-Lauritsen LB, Pin JP, Kniazeff J (2018) Allosteric interactions between GABA(B1) subunits control orthosteric binding sites occupancy within GABA(B) oligomers. Neuropharmacology 136(Pt A):92–101 - PubMed
  212. Sturchler E, Li X, de Lourdes Ladino M, Kaczanowska K, Cameron M, Griffin PR, Finn MG, Markou A, McDonald P (2017) GABA(B) receptor allosteric modulators exhibit pathway-dependent and species-selective activity. Pharmacol Res Perspect 5(2):e00288 - PubMed
  213. Sun B, Chen L, Liu L, Xia Z, Pin JP, Nan F, Liu J (2016) A negative allosteric modulator modulates GABAB-receptor signalling through GB2 subunits. Biochem J 473(6):779–787 - PubMed
  214. Sun Z, Sun L, Tu L (2020) GABAB receptor-mediated PI3K/Akt signaling pathway alleviates oxidative stress and neuronal cell injury in a rat model of Alzheimer’s disease. J Alzheimers Dis 76(4):1513–1526 - PubMed
  215. Symonds E, Butler R, Omari T (2003) The effect of the GABAB receptor agonist baclofen on liquid and solid gastric emptying in mice. Eur J Pharmacol 470(1–2):95–97 - PubMed
  216. Szabadi E (2015) GHB for cataplexy: possible mode of action. J Psychopharmacol 29(6):744–749 - PubMed
  217. Tabata T, Araishi K, Hashimoto K, Hashimotodani Y, van der Putten H, Bettler B, Kano M (2004) Ca2+ activity at GABAB receptors constitutively promotes metabotropic glutamate signaling in the absence of GABA. Proc Natl Acad Sci U S A 101(48):16952–16957 - PubMed
  218. Teichgräber LA, Lehmann TN, Meencke HJ, Weiss T, Nitsch R, Deisz RA (2009) Impaired function of GABA(B) receptors in tissues from pharmacoresistant epilepsy patients. Epilepsia 50(7):1697–1716 - PubMed
  219. Tian J, Dang H, Hu A, Xu W, Kaufman DL (2017) Repurposing lesogaberan to promote human islet cell survival and β-cell replication. J Diabetes Res 2017:6403539 - PubMed
  220. Tsunekawa T, Banno R, Yaginuma H, Taki K, Mizoguchi A, Sugiyama M, Onoue T, Takagi H, Hagiwara D, Ito Y, Iwama S, Goto M, Suga H, Bettler B, Arima H (2019) GABA(B) receptor signaling in the mesolimbic system suppresses binge-like consumption of a high-fat diet. IScience 20:337–347 - PubMed
  221. Tu H, Rondard P, Xu C, Bertaso F, Cao F, Zhang X, Pin JP, Liu J (2007) Dominant role of GABAB2 and Gbetagamma for GABAB receptor-mediated-ERK1/2/CREB pathway in cerebellar neurons. Cell Signal 19(9):1996–2002 - PubMed
  222. Tyagi RK, Bisht R, Pant J, Kumar P, Majeed AB, Prakash A (2015) Possible role of GABA-B receptor modulation in MPTP induced Parkinson’s disease in rats. Exp Toxicol Pathol 67(2):211–217 - PubMed
  223. Urwyler S (2011) Allosteric modulation of family C G-protein-coupled receptors: from molecular insights to therapeutic perspectives. Pharmacol Rev 63(1):59–126 - PubMed
  224. Urwyler S, Mosbacher J, Lingenhoehl K, Heid J, Hofstetter K, Froestl W, Bettler B, Kaupmann K (2001) Positive allosteric modulation of native and recombinant gamma-aminobutyric acid(B) receptors by 2,6-Di-tert-butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930) and its aldehyde analog CGP13501. Mol Pharmacol 60(5):963–971 - PubMed
  225. Urwyler S, Pozza MF, Lingenhoehl K, Mosbacher J, Lampert C, Froestl W, Koller M, Kaupmann K (2003) N,N′-Dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine (GS39783) and structurally related compounds: novel allosteric enhancers of gamma-aminobutyric acidB receptor function. J Pharmacol Exp Ther 307(1):322–330 - PubMed
  226. Urwyler S, Gjoni T, Kaupmann K, Pozza MF, Mosbacher J (2004) Selected amino acids, dipeptides and arylalkylamine derivatives do not act as allosteric modulators at GABAB receptors. Eur J Pharmacol 483(2–3):147–153 - PubMed
  227. Urwyler S, Gjoni T, Koljatic J, Dupuis DS (2005) Mechanisms of allosteric modulation at GABAB receptors by CGP7930 and GS39783: effects on affinities and efficacies of orthosteric ligands with distinct intrinsic properties. Neuropharmacology 48(3):343–353 - PubMed
  228. Vanhoose AM, Emery M, Jimenez L, Winder DG (2002) ERK activation by G-protein-coupled receptors in mouse brain is receptor identity-specific. J Biol Chem 277(11):9049–9053 - PubMed
  229. Veenstra-VanderWeele J, Cook EH, King BH, Zarevics P, Cherubini M, Walton-Bowen K, Bear MF, Wang PP, Carpenter RL (2017) Arbaclofen in children and adolescents with autism spectrum disorder: a randomized, controlled, phase 2 trial. Neuropsychopharmacology 42(7):1390–1398 - PubMed
  230. Vigot R, Barbieri S, Bräuner-Osborne H, Turecek R, Shigemoto R, Zhang YP, Luján R, Jacobson LH, Biermann B, Fritschy JM, Vacher CM, Müller M, Sansig G, Guetg N, Cryan JF, Kaupmann K, Gassmann M, Oertner TG, Bettler B (2006) Differential compartmentalization and distinct functions of GABAB receptor variants. Neuron 50(4):589–601 - PubMed
  231. Vlachou S, Paterson NE, Guery S, Kaupmann K, Froestl W, Banerjee D, Finn MG, Markou A (2011) Both GABA(B) receptor activation and blockade exacerbated anhedonic aspects of nicotine withdrawal in rats. Eur J Pharmacol 655(1–3):52–58 - PubMed
  232. Weatherby RP, Allan RD, Johnston GA (1984) Resolution of the stereoisomers of baclofen by high performance liquid chromatography. J Neurosci Methods 10(1):23–28 - PubMed
  233. Wellendorph P, Høg S, Greenwood JR, de Lichtenberg A, Nielsen B, Frølund B, Brehm L, Clausen RP, Bräuner-Osborne H (2005) Novel cyclic gamma-hydroxybutyrate (GHB) analogs with high affinity and stereoselectivity of binding to GHB sites in rat brain. J Pharmacol Exp Ther 315(1):346–351 - PubMed
  234. Wong CG, Gibson KM, Snead OC 3rd (2004) From the street to the brain: neurobiology of the recreational drug gamma-hydroxybutyric acid. Trends Pharmacol Sci 25(1):29–34 - PubMed
  235. Young SZ, Bordey A (2009) GABA’s control of stem and cancer cell proliferation in adult neural and peripheral niches. Physiology 24:171–185 - PubMed
  236. Zhang X, Du Z, Liu J, He J (2014) Gamma-aminobutyric acid receptors affect the progression and migration of tumor cells. J Recept Signal Transduct Res 34(6):431–439 - PubMed
  237. Zhang W, Xu C, Tu H, Wang Y, Sun Q, Hu P, Hu Y, Rondard P, Liu J (2015) GABAB receptor upregulates fragile X mental retardation protein expression in neurons. Sci Rep 5(1):10468 - PubMed
  238. Zuo H, Glaaser I, Zhao Y, Kurinov I, Mosyak L, Wang H, Liu J, Park J, Frangaj A, Sturchler E, Zhou M, McDonald P, Geng Y, Slesinger PA, Fan QR (2019) Structural basis for auxiliary subunit KCTD16 regulation of the GABA(B) receptor. Proc Natl Acad Sci U S A 116(17):8370–8379 - PubMed

Publication Types