Characterization of (R,S)-5,7-di-tert-butyl-3-hydroxy-3-trifluoromethyl-3H- benzofuran-2-one as a positive allosteric modulator of GABA B receptors

British Journal of Pharmacology

Volumn 154, Issue 4, 2008, Pages 797-811

  Malherbe, P ^a   Masciadri, R ^a,b   Norcross, R D ^a   Knoflach, F ^a   Kratzeisen, C ^a   Zenner, M T ^a   Kolb, Y ^a   Marcuz, A ^a   Huwyler, J ^a,c   Nakagawa, T ^a,d   Porter, R H P ^a   Thomas, A W ^a   Wettstein, J G ^a   Sleight, A J ^a   Spooren, W ^a   Prinssen, E P ^a  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

^b ETH ZURICH   (Switzerland)

^c UNIVERSITY OF APPLIED SCIENCES AND ARTS NORTHWESTERN SWITZERLAND   (Switzerland)

^d CHUGAI PHARMACEUTICAL CO LTD   (Japan)

Author keywords

Anxiety; Class C GPCR; GABA B receptor; Loss of righting reflex; Population spike; Positive allosteric modulator; rac BHFF; Stress induced hyperthermia

Indexed keywords

2,6 DI TERT BUTYL 4 (3 HYDROXY 2,2 DIMETHYLPROPYL)PHENOL; 4 AMINOBUTYRIC ACID B RECEPTOR; 4 AMINOBUTYRIC ACID B RECEPTOR STIMULATING AGENT; 5,7 DI TERT BUTYL 3 HYDROXY 3 TRIFLUOROMETHYL 3H BENZOFURAN 2 ONE; BACLOFEN; GUANOSINE 5' O (3 THIOTRIPHOSPHATE); SULFUR 35;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ANXIETY; ARTICLE; BINDING AFFINITY; CALCIUM MOBILIZATION; CHO CELL; CONTROLLED STUDY; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG HYDROLYSIS; DRUG POTENCY; DRUG POTENTIATION; DRUG SPECIFICITY; DRUG STRUCTURE; FLUOROMETRY; HYPERTHERMIA; LIQUID CHROMATOGRAPHY; LOCOMOTION; MALE; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; PHARMACODYNAMICS; PRIORITY JOURNAL; RAT; RIGHTING REFLEX; STRESS; STRESS INDUCED HYPERTHERMIA; TANDEM MASS SPECTROMETRY;

ALLOSTERIC REGULATION; ANIMALS; ANTI-ANXIETY AGENTS; BACLOFEN; BENZOFURANS; CHO CELLS; CRICETINAE; CRICETULUS; DOSE-RESPONSE RELATIONSHIP, DRUG; GABA AGONISTS; GTP-BINDING PROTEIN GAMMA SUBUNITS; HUMANS; MALE; MICE; MICE, INBRED DBA; PYRAMIDAL CELLS; RATS; RATS, WISTAR; RECEPTORS, GABA-B; REFLEX; STEREOISOMERISM;

EID: 44949115930     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1038/bjp.2008.135     Document Type: Article

References (43)

1. Bettler B, Kaupmann K, Mosbacher J, Gassmann M (2004). Molecular structure and physiological functions of GABA(B) receptors. Physiol Rev 84: 835-867.
2. 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: 29085-29091.
3. Bouwknecht JA, Olivier B, Paylor RE (2007). The stress-induced hyperthermia paradigm as a physiological animal model for anxiety: a review of pharmacological and genetic studies in the mouse. Neurosci Biobehav Rev 31: 41-59.
4. Bowery NG (2006). GABA(B) receptor: a site of therapeutic benefit. Curr Opin Pharmacol 6: 37-43.
5. Breslow MF, Frankhauser MP, Potter RL, Meredith KE, Misiaszek J, Hope DG (1989). Role of g-aminobutyric acid in antipanic drug efficacy. Am J Psychiatry 146: 353-356.
6. Calver AR, Medhurst AD, Robbins MJ, Charles KJ, Evans ML, Harrison DC et al. (2000). The expression of GABA(B1) and GABA(B2) receptor subunits in the CNS differs from that in peripheral tissues. Neuroscience 100: 155-170.
7. Cange L, Johnsson E, Rydholm H, Lehmann A, Finizia C, Lundell L et al. (2002). Baclofen-mediated gastro-oesophageal acid reflux control in patients with established reflux disease. Aliment Pharmacol Ther 16: 869-873.
8. Carai MA, Colombo G, Froestl W, Gessa GL (2004). In vivo effectiveness of CGP7930, a positive allosteric modulator of the GABAB receptor. Eur J Pharmacol 504: 213-216.
9. Chen Y, Menendez-Roche N, Sher E (2006). Differential modulation by the GABAB receptor allosteric potentiator 2,6-di-tert-butyl-4-(3-hydroxy-2,2- dimethylpropyl)-phenol (CGP7930) of synaptic transmission in the rat hippocampal CA1 area. J Pharmacol Exp Ther 317: 1170-1177.
10. Chen Y, Phillips K, Minton G, Sher E (2005). GABA(B) receptor modulators potentiate baclofen-induced depression of dopamine neuron activity in the rat ventral tegmental area. Br J Pharmacol 144: 926-932.
11. Cryan JF, Kelly PH, Chaperon F, Gentsch C, Mombereau C, Lingenhoehl K et al. (2004). Behavioral characterization of the novel GABAB receptor-positive modulator GS39783 (N,N′-dicyclopentyl-2- methylsulfanyl-5-nitro-pyrimidine-4,6-diamine): anxiolyticlike activity without side effects associated with baclofen or benzodiazepines. J Pharmacol Exp Ther 310: 952-963.
12. Drake RG, Davis LL, Cates ME, Jewell ME, Ambrose SM, Lowe JS (2003). Baclofen treatment for chronic posttraumatic stress disorder. Ann Pharmacother 37: 1177-1181.
13. Frankowska M, Filip M, Przegaliñski E (2007). Effects of GABAB receptor ligands in animal tests of depression and anxiety. Pharmacol Rep 59: 645-655.
14. Galvez T, Prezeau L, Milioti G, Franek M, Joly C, Froestl W et al. (2000). Mapping the agonist-binding site of GABAB type 1 subunit sheds light on the activation process of GABAB receptors. J Biol Chem 275: 41166-41174.
15. Gjoni T, Desrayaud S, Imobersteg S, Urwyler S (2006). The positive allosteric modulator GS39783 enhances GABA(B) receptor-mediated inhibition of cyclic AMP formation in rat striatum in vivo. J Neurochem 96: 1416-1422.
16. 2+ receptor expressed in Xenopus laevis oocytes by NPS 467 or NPS 568. Mol Pharmacol 53: 1083-1088.
17. Havlickova M, Prezeau L, Duthey B, Bettler B, Pin JP, Blahos J (2002). The intracellular loops of the GB2 subunit are crucial for G-protein coupling of the heteromeric gamma-aminobutyrate B receptor. Mol Pharmacol 62: 343-350.
18. Hill DR, Bowery NG (1981). 3H-Baclofen and 3H-GABA bind to bicuculline-insensitive GABA B sites in rat brain. Nature 290: 149-152.
19. Jacobson LH, Cryan JF (2005). Differential sensitivity to the motor and hypothermic effects of the GABA B receptor agonist baclofen in various mouse strains. Psychopharmacology (Berl) 179: 688-699.
20. Johnson MP, Baez M, Jagdmann Jr GE, Britton TC, Large TH, Callagaro DO et al. (2003). Discovery of allosteric potentiators for the metabotropic glutamate 2 receptor: synthesis and subtype selectivity of N-(4-(2- methoxyphenoxy)phenyl)-N-(2,2,2-trifluoroethylsulfonyl) pyrid-3-ylmethylamine. J Med Chem 46: 3189-3192.
21. Kaupmann K, Huggel K, Heid J, Flor PJ, Bischoff S, Mickel SJ et al. (1997). Expression cloning of GABA(B) receptors uncovers similarity to metabotropic glutamate receptors [see comments]. Nature 386: 239-246.
22. Kaupmann K, Malitschek B, Schuler V, Heid J, Froestl W, Beck P et al. (1998). GABA(B)-receptor subtypes assemble into functional heteromeric complexes. Nature 396: 683-687.
23. Kinney GG, O'Brien JA, LemaireW, Burno M, Bickel DJ, Clements MK et al. (2005). A novel selective positive allosteric modulator of metabotropic glutamate receptor subtype 5 has in vivo activity and antipsychotic-like effects in rat behavioral models. J Pharmacol Exp Ther 313: 199-206.
24. 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: 7352-7361.
25. Knoflach F, Mutel V, Jolidon S, Kew JN, Malherbe P, Vieira E et al. (2001). Positive allosteric modulators of metabotropic glutamate 1 receptor: characterization, mechanism of action, and binding site. Proc Natl Acad Sci USA 98: 13402-13407.
26. Malherbe P, Knoflach F, Broger C, Ohresser S, Kratzeisen C, Adam G et al. (2001). Identification of essential residues involved in the glutamate binding pocket of the group II metabotropic glutamate receptor. Mol Pharmacol 60: 944-954.
27. Malherbe P, Masciadri R, Norcross RD, Prinssen E (2007). US patent 2007027204. Chem Abstr Can 146: 184345.
28. 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: 1050-1062.
29. Mombereau C, Kaupmann K, Gassmann M, Bettler B, van der Putten H, Cryan JF (2005). Altered anxiety and depression-related behaviour in mice lacking GABAB(2) receptor subunits. NeuroReport 16: 307-310.
30. Muhlemann A, Ward NA, Kratochwil N, Diener C, Fischer C, Stucki A et al. (2006). Determination of key amino acids implicated in the actions of allosteric modulation by 3,3′-difluorobenzaldazine on rat mGlu5 receptors. Eur J Pharmacol 529: 95-104.
31. Partyka A, K"odziñska A, Szewczyk B, Wieroñska JM, Chojnacka-Wójcik E, Librowski T et al. (2007). Effects of GABAB receptor ligands in rodent tests of anxiety-like behavior. Pharmacol Rep 59: 757-762.
32. Pehrson R, Lehmann A, Andersson KE (2002). Effects of gamma-aminobutyrate B receptor modulation on normal micturition and oxyhemoglobin induced detrusor overactivity in female rats. J Urol 168: 2700-2705.
33. Perez-Garci E, Gassmann M, Bettler B, Larkum ME (2006). The GABA(B1b) isoform mediates long-lasting inhibition of dendritic Ca(2+) spikes in layer 5 somatosensory pyramidal neurons. Neuron 50: 603-616.
34. 2+-sensing receptor interact within overlapping but not identical binding sites in the transmembrane domain modeling and mutagenesis of the binding site of Calhex 231, a novel negative allosteric modulator of the extracellular Ca(2+)-sensing receptor. J Biol Chem 279: 18990-18997.
35. Pilc A, Nowak G (2005). GABAergic hypotheses of anxiety and depression: focus on GABA-B receptors. Drugs Today 41: 755-766.
36. Pin JP, Galvez T, Prezeau L (2003). Evolution, structure, and activation mechanism of family 3/C G-protein-coupled receptors. Pharmacol Ther 98: 325-354.
37. Pin JP, Kniazeff J, Liu J, Binet V, Goudet C, Rondard P et al. (2005). Allosteric functioning of dimeric class C G-protein-coupled receptors. FEBS J 272: 2947-2955.
38. Piqueras L, Martinez V, Symonds E, Butler R, Omari T (2004). Peripheral GABAB agonists stimulate gastric acid secretion in mice: the effect of the GABAB receptor agonist baclofen on liquid and solid gastric emptying in mice. Br J Pharmacol 142: 1038-1048.
39. Spooren WP, Schoeffter P, Gasparini F, Kuhn R, Gentsch C (2002). Pharmacological and endocrinological characterisation of stress-induced hyperthermia in singly housed mice using classical and candidate anxiolytics (LY314582, MPEP and NKP608). Eur J Pharmacol 435: 161-170.
40. Urwyler S, Mosbacher J, Lingenhoehl K, Heid J, Hofstetter K, Froestl W et al. (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: 963-971.
41. Urwyler S, Pozza MF, Lingenhoehl K, Mosbacher J, Lampert C, Froestl W et al. (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: 322-330.
42. Vacher CM, Bettler B (2003). GABA(B) receptors as potential therapeutic targets. Curr Drug Target CNS Neurol Disord 2: 248-259.
43. Vigot R, Barbieri S, Brauner-Osborne H, Turecek R, Shigemoto R, Zhang YP et al. (2006). Differential compartmentalization and distinct functions of GABA(B) receptor variants. Neuron 50: 589-601.