3-Hydroxy-2′-methoxy-6-methylflavone: A potent anxiolytic with a unique selectivity profile at GABA A receptor subtypes

Biochemical Pharmacology

Volumn 82, Issue 12, 2011, Pages 1971-1983

  Karim, Nasiara ^a   Gavande, Navnath ^a   Wellendorph, Petrine ^c   Johnston, Graham A R ^b   Hanrahan, Jane R ^a   Chebib, Mary ^a  

^a UNIVERSITY OF SYDNEY   (Australia)

^b University of Sydney   (Australia)

^c UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

Allosteric activation; Allosteric modulation; Anxiolytics; Flavonoids; GABA A receptors

Indexed keywords

3 HYDROXY 20 METHOXY 6 METHYLFLAVONE; 4 AMINOBUTYRIC ACID A RECEPTOR; 4 AMINOBUTYRIC ACID A RECEPTOR ALPHA4; 4 AMINOBUTYRIC ACID A RECEPTOR ALPHA6; 4 AMINOBUTYRIC ACID A RECEPTOR BETA1; 4 AMINOBUTYRIC ACID A RECEPTOR DELTA3; ANXIOLYTIC AGENT; BICUCULLINE; DIAZEPAM; FLUMAZENIL; UNCLASSIFIED DRUG;

ACUTE TOXICITY; AGGRESSION; ALLOSTERISM; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANXIETY DISORDER; ARTICLE; CONCENTRATION (PARAMETERS); CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFICACY; DRUG HYPERSENSITIVITY; DRUG MEGADOSE; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; ELECTRIC CURRENT; FEMALE; IRRITABILITY; LOCOMOTION; MALE; MAZE TEST; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RIGHTING REFLEX; SLEEP TIME; TOXICITY TESTING; TRANQUILIZING ACTIVITY; XENOPUS;

ANIMALS; ANTI-ANXIETY AGENTS; DIAZEPAM; DOSE-RESPONSE RELATIONSHIP, DRUG; FATTY ACIDS, VOLATILE; FLAVONES; FLUMAZENIL; GAMMA-AMINOBUTYRIC ACID; HUMANS; MALE; MICE; MICE, INBRED BALB C; MOLECULAR STRUCTURE; MOTOR ACTIVITY; OOCYTES; PENTYLENETETRAZOLE; RECEPTORS, GABA-A; RECOMBINANT PROTEINS; THIOPENTAL; XENOPUS;

EID: 80555150631     PISSN: 00062952     EISSN: 18732968     Source Type: Journal    
DOI: 10.1016/j.bcp.2011.09.002     Document Type: Article

References (64)

1. E.A. Barnard, P. Skolnick, R.W. Olsen, H. MÖhler, W. Sieghart, and G. Biggio International Union of Pharmacology XV. Subtypes of gamma-aminobutyric acidA receptors: classification on the basis of subunit structure and receptor function Pharmacol Rev 50 1998 291 313 (Pubitemid 28304030)
2. A receptors Nat Rev Neurosci 6 2005 215 229 (Pubitemid 40342416)
3. A receptor genes in the human genome J Biol Chem 279 2004 41422 41435 (Pubitemid 39313583)
4. R.W. Olsen, and W. Sieghart International Union of Pharmacology LXX. Subtypes of gamma-aminobutyric acid(A) receptors: classification on the basis of subunit composition, pharmacology, and function. Update Pharmacol Rev 60 2008 243 260
5. A-receptor subtypes really occur in the brain? Trends Neurosci 19 1996 139 143
6. A receptor channel pharmacology Curr Pharm Design 11 2005 1867 1885 (Pubitemid 40766848)
7. A receptor subtypes: clinical efficacy and selectivity of benzodiazepine site ligands Ann Med 29 1997 275 282 (Pubitemid 27399946)
8. C. Braestrup, M. Nielsen, T. Honoré, L.H. Jensen, and E.N. Petersen Benzodiazepine receptor ligands with positive and negative efficacy Neuropharmacology 22 1983 1451 1457 (Pubitemid 14175493)
9. C.R. Gardner, W.R. Tully, and C.J.R. Hedgecock The rapidly expanding range of neuronal benzodiazepine receptor ligands Prog Neurobiol 40 1993 1 61
10. T.B.C. Johnstone, D.J. Hogenkamp, L. Coyne, J. Su, R.F. Halliwell, and M.B. Tran Modifying quinolone antibiotics yields new anxiolytics Nat Med 10 2004 31 32 (Pubitemid 38524695)
11. A receptor subtype-selective modulators I. α2/α3-Selective agonists as non-sedating anxiolytics Curr Top Med Chem 11 9 2011 1176 1202
12. U. Rudolph, F. Crestani, D. Benke, I. Brünig, J.A. Benson, and J.M. Fritschy Benzodiazepine actions mediated by specific γ-aminobutyric acid(A) receptor subtypes Nature 401 1999 796 800
13. K. Low, F. Crestani, R. Keist, D. Benke, I. Brunig, and J.A. Benson Molecular and neuronal substrate for the selective attenuation of anxiety Science 290 2000 131 134
14. A receptor α1 subtype Nat Neurosci 3 2000 587 592 (Pubitemid 30332078)
15. H. MÖhler, J.M. Fritschy, and U. Rudolph A new benzodiazepine pharmacology J Pharmacol Exp Ther 300 2002 2 8 (Pubitemid 34028501)
16. A receptor subtypes mediate the anxiolytic properties of benzodiazepine site ligands in the conditioned emotional response paradigm Eur J Neurosci 23 2006 2495 2504 (Pubitemid 43742880)
17. J.B. Harborne, and C.A. Williams Advances in flavonoid research since 1992 Phytochemistry 55 2000 481 504
18. G. Griebel, G. Perrault, S. Tan, H. Schoemaker, and D.J. Sanger Pharmacological studies on synthetic flavonoids: comparison with diazepam Neuropharmacology 38 1999 965 977 (Pubitemid 29240613)
19. K.M. Hui, M.S.Y. Huen, H.Y. Wang, H. Zheng, E. Sigel, and R. Baur Anxiolytic effect of wogonin, a benzodiazepine receptor ligand isolated from Scutellaria baicalensis Georgi Biochem Pharmacol 64 2002 1415 1424 (Pubitemid 35248258)
20. A receptor complex Curr Drug Targets CNS Neurol Disord 4 2005 575 585 (Pubitemid 41448383)
21. S.P. Fernandez, M. Nguyen, T.T. Yow, C. Chu, G.A. Johnston, and J.R. Hanrahan The flavonoid glycosides, myricitrin, gossypin and naringin exert anxiolytic action in mice Neurochem Res 34 2009 1867 1875
22. A receptors with higher efficacy for the α2 subtype and anxiolytic action in mice Neuropharmacology 55 2008 900 907
23. A receptors Eur J Pharmacol 49 2004 1 8 (Pubitemid 38501769)
24. M. Nielsen, S. Frøkjær, and C. Braestrup High affinity of the naturally-occurring biflavonoid, amentoflavon, to brain benzodiazepine receptors in vitro Biochem Pharmacol 37 1988 3285 3287
25. A receptor Eur J Pharmacol 519 2005 199 207 (Pubitemid 41278538)
26. A receptors in vitro Br J Pharmacol 162 2011 1326 1339
27. J.E. Gowan, P.M. Hayden, and T.S. Wheeler A new synthesis of flavonols J Chem Soc 1955 862 866
28. J.A. Ballantine, and W.B. Whalley Aluminium complexes of flavonols J Chem Soc 1956 3224 3226
29. A receptors expressed in Xenopus oocytes Eur J Pharmacol 512 2005 97 104 (Pubitemid 40552793)
30. P. Wellendorph, S. Høg, J.R. Greenwood, A. de Lichtenberg, B. Nielsen, and B. Frølund Novel cyclic γ-hydroxybutyrate (GHB) analogs with high affinity and stereoselectivity of binding to GHB sites in rat brain J Pharmacol Exp Ther 315 2005 346 351 (Pubitemid 41380530)
31. S. Irwin comprehensive observational assessment: 1a. A systematic, quantitative procedure for assessing the behavioural and physiological state of the mouse Psychopharmacologia 13 1968 222 257
32. C antagonists inhibit myopia development and facilitate learning and memory J Pharmacol Exp Ther 328 2009 448 457
33. S. File, and S. Pellow The effects of triazolobenzodiazepines in two animal tests of anxiety and in the holeboard Br J Pharmacol 86 1985 729 735 (Pubitemid 16235389)
34. M. Bourin, and M. Hascoet The mouse light/dark box test Eur J Pharmacol 463 2003 55 65 (Pubitemid 36205072)
35. R. Ferrini, G. Miragoli, and B. Taccardi Neuro-pharmacological studies on SB 5833, a new psychotherapeutic agent of the benzodiazepine class Arzneimittelforschung 24 1974 2029 2032
36. E. Bonetti, L. Pierri, R. Cumin, M. Schaffner, E. Gamzu, and R. Muller Benzodiazepine antagonist RO 15-1788: neurological and behavioral effects Psychopharmacology 78 1982 8 18 (Pubitemid 12036012)
37. A receptors are differentially sensitive to zinc: dependence on subunit composition Br J Pharmacol 103 1991 1837 1839
38. A receptors: functional selectivity for extrasynaptic receptors is dependent on the absence of gamma2 J Pharmacol Exp Ther 316 2006 1351 1359 (Pubitemid 43345312)
39. A receptor subtype selectivity underlying anxiolytic effect of 6-hydroxyflavone Biochem Pharmacol 79 2010 1337 1344
40. N. Karim, J. Curmi, N. Gavande, G.A.R. Johnston, J.R. Hanrahan, and M.L. Tierney 2′-Methoxy-6-methylflavone: a novel anxiolytic and sedative with subtype selective activating and modulating actions at GABA-A receptors Br J Pharmacol 2011 10.1111/j.1476-5381.2011.01604.x [Epub ahead of print]
41. A.J. Smith, B. Oxley, S. Malpas, G.V. Pillai, and P.B. Simpson Compounds exhibiting selective efficacy for different β subunits of human recombinant γ-aminobutyric acidA receptors J Pharmacol Exp Ther 311 2004 601 609 (Pubitemid 39391545)
42. A receptors containing the delta subunit J Neurosci 22 2002 1541 1549 (Pubitemid 35386273)
43. A receptors Mol Pharmacol 66 2004 1517 1522
44. K.A. Youdim, B. Shukitt-Hale, and J.A. Joseph Flavonoids and the brain: interactions at the blood-brain barrier and their physiological effects on the central nervous system Free Radic Biol Med 37 2004 1683 1693 (Pubitemid 39441053)
45. D. Kavvadias, P. Sand, K.A. Youdim, M.Z. Qaiser, C. Rice-Evans, and R. Baur The flavone hispidulin, a benzodiazepine receptor ligand with positive allosteric properties, traverses the blood-brain barrier and exhibits anticonvulsive effects Br J Pharmacol 142 2004 811 820 (Pubitemid 38998095)
46. P. Zanoli, R. Avallone, and M. Baraldi Behavioral characterisation of the flavonoids apigenin and chrysin Fitoterapia 71 Suppl. 1 2000 S117 S123
47. A.A. Walf, and C.A. Frye The use of the elevated plus maze as an assay of anxiety-related behavior in rodents Nat Protocols 2 2007 322 328 (Pubitemid 47040046)
48. J.N. Crawley Exploratory behavior models of anxiety in mice Neurosci Biobehav Rev 9 1985 37 44 (Pubitemid 15136669)
49. A receptors reduces actions of alcohol and other drugs J Pharmacol Exp Ther 304 2003 30 36 (Pubitemid 36008909)
50. M.D. Majewska, N.L. Harrison, R.D. Schwartz, J.L. Barker, and S.M. Paul Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor Science 232 1986 1004 1007 (Pubitemid 16085410)
51. A receptor Nat Rev Neurosci 6 2005 565 575 (Pubitemid 40942823)
52. R.M. Mihalek, P.K. Banerjee, E.R. Korpi, J.J. Quinlan, L.L. Firestone, and Z.-P. Mi Attenuated sensitivity to neuroactive steroids in γ-aminobutyrate type A receptor delta subunit knockout mice Proc Natl Acad Sci USA 96 1999 12905 12910 (Pubitemid 29513601)
53. R. Hoehn-Saric Effects of THIP on chronic anxiety Psychopharmacology (Berl) 80 1983 338 341
54. A receptor subtypes Pharmacol Ther 112 2006 513 528 (Pubitemid 44488711)
55. A receptors Neuropharmacology 58 2010 702 711
56. A receptors Proc Natl Acad Sci USA 99 2002 8980 8985 (Pubitemid 34693669)
57. F. Crestani, K. Low, R. Keist, M. Mandelli, H. MÖhler, and U. Rudolph Molecular targets for the myorelaxant action of diazepam Mol Pharmacol 59 2001 442 445 (Pubitemid 32179921)
58. A receptors, is a nonsedating anxiolytic in rodents and primates J Pharmacol Exp Ther 316 2006 410 422 (Pubitemid 41832621)
59. A receptor subtypes reduces ataxia J Pharmacol Exp Ther 332 2010 1040 1053
60. A receptor activity Nat Neurosci 8 2005 339 345 (Pubitemid 40300191)
61. A receptors as a target for the development of novel anxiolytics Expert Opin Investig Drugs 14 2005 601 618 (Pubitemid 40790282)
62. A receptors: a viable target for novel anxiolytics? Curr Opin Pharmacol 6 2006 24 29 (Pubitemid 43103816)
63. A receptor modulator Proc Natl Acad Sci USA 102 2005 7380 7385 (Pubitemid 40696386)
64. A receptors different from diazepam Neuropharmacology 52 2007 796 801 (Pubitemid 46227470)