Pharmacophore/receptor models for GABA(A)/BzR subtypes (α1β3γ2, α5β3γ2, and α6β3γ2) via a comprehensive ligand-mapping approach

Journal of Medicinal Chemistry

Volumn 43, Issue 1, 2000, Pages 71-95

  Huang, Qi ^a   He, Xiaohui ^a   Ma, Chunrong ^a   Liu, Ruiyan ^a   Yu, Shu ^a   Dayer, Charlotte A ^b   Wenger, Galen R ^b   McKernan, Ruth ^c   Cook, James M ^a  

^a UNIVERSITY OF WISCONSIN MILWAUKEE   (United States)

^b UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES   (United States)

^c NEUROSCIENCE RESEARCH CENTRE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

2 (4 CHLOROPHENYL) 5H PYRAZOLO[4,3 C]QUINOLIN 3 ONE; 2 PHENYL 5H PYRAZOLO[4,3 C]QUINOLIN 3 ONE; 3 METHYL 6 (3 TRIFLUOROMETHYLPHENYL) 1,2,4 TRIAZOLO[4,3 B]PYRIDAZINE; 4 AMINOBUTYRIC ACID A RECEPTOR; 6 BENZYLOXY 4 METHOXYMETHYL BETA CARBOLINE 3 CARBOXYLIC ACID ETHYL ESTER; 7 CHLORO 5,6 DIHYDRO 3 (5 ISOPROPYL 1,2,4 OXADIAZOL 3 YL) 5 METHYL 4H IMIDAZO[1,5 A][1,4]BENZODIAZEPIN 6 ONE; 8 AZIDO 5,6 DIHYDRO 5 METHYL 6 OXO 4H IMIDAZO[1,5 A][1,4]BENZODIAZEPINE 3 CARBOXYLIC ACID ETHYL ESTER; BENZODIAZEPINE DERIVATIVE; BENZODIAZEPINE RECEPTOR; BETA CARBOLINE DERIVATIVE; BRETAZENIL; DIAZEPAM; FLUNITRAZEPAM; IMIDAZOLE DERIVATIVE; INDOLE DERIVATIVE; PYRAZOLONE DERIVATIVE; PYRIMIDINE DERIVATIVE; QUINOLINE DERIVATIVE; RECEPTOR SUBTYPE; RY 23; RY 24; RY 80; TRIAZOLAM; TRIAZOLINE DERIVATIVE; UNCLASSIFIED DRUG; ZOLPIDEM;

ANIMAL EXPERIMENT; ARTICLE; BINDING AFFINITY; BRAIN; COMPUTER MODEL; DRUG BINDING SITE; DRUG RECEPTOR BINDING; HIPPOCAMPUS; LIGAND BINDING; MONKEY; NERVOUS SYSTEM; NEUROPHARMACOLOGY; NEUROTRANSMISSION; NONHUMAN; PIGEON; RAT;

ANIMALS; BENZODIAZEPINES; CARBOLINES; CELL LINE; COLUMBIDAE; CONDITIONING, OPERANT; CRYSTALLOGRAPHY, X-RAY; HUMANS; INDOLES; LIGANDS; MALE; MODELS, MOLECULAR; PYRIMIDINES; QUINOLONES; RADIOLIGAND ASSAY; RECEPTORS, GABA-A; SAIMIRI; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0034642556     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm990341r     Document Type: Article

References (177)

1. Möhler, H.; Okada, T. Benzodiazepine receptors: demonstration in the central nervous system. Science 1977, 198, 849-851.
2. Squires, R. F.; Braestrup, C. Benzodiazepine receptors in rat brain. Nature 1977, 266, 732-734.
3. Gavish, M.; Snyder, S. H. Soluble benzodiazepine receptors: GABAergic regulation. Life Sci. 1980, 26, 579-582.
4. Gavish, M.; Snyder, S. H. Gamma-aminobutyric acid and benzodiazepine receptors: copurification and characterization. Proc. Natl. Acad. Sci. U.S.A. 1981, 78, 1939-1942.
5. Ninan, P. T.; Insel, T. M.; Cohen, R. M.; Cook, J. M.; Skolnick, P.; Paul, S. M. Benzodiazepine receptor-mediated experimental "anxiety" in primates. Science 1962, 218, 1332-1334.
6. Wong, G.; Skolnick, P. High affinity ligands for 'diazepaminsensitive' benzodiazepine receptors. Eur. J. Pharmacol. Mol. Pharmacol. Sect. 1992, 225, 63-68.
7. Mendelson, W. B.; Cain, M.; Cook, J. M.; Paul, S. M.; Skolnick, P. A benzodiazepine receptor antagonist decreases sleep and reverses the hypnotic actions of flurazepam. Science 1983, 219, 414-416.
8. Venault, P.; Chapouthier, G.; de-Carvalho, L. P.; Simiand, J.; Morre, M.; Dodd, R. H.; Rossier, J. Benzodiazepine impairs and β-carboline enhances performance in learning and memory tasks. Nature 1986, 321, 864-866.
9. A receptor subtypes. Pharm. Rev. 1995, 47, 181-234.
10. A receptor subunit. Nature 1997, 385, 820-823.
11. A receptors depend on subunit composition. Neuron 1990, 4, 919-928.
12. A receptors on channel function. Neuron 1990, 5, 703-711.
13. A receptor populations with novel subunit combinations and drug binding profiles identified in brain by α5- and δ-subunit-specific immunopurification. J. Biol. Chem. 1993, 268, 5965-5973.
14. Benavides, J.; Peny, B.; Ruano, D.; Vitorica, J.; Scatton, B. Comparative autoradiographic distribution on central ω (benzodiazepine) modulatory site subtypes with high, intermediate, and low affinity for zolpidem and alpidem. Brain Res. 1993, 604, 240-250.
15. A receptor. J. Neurosci. 1996, 16, 5415-5424.
16. 3H]Ro 15-4513: A biochemical and autoradiographic study. J. Neurochem. 1987, 48, 46-52.
17. A receptor α4-subunit. FEBS Lett. 1991, 289, 227-230.
18. Gu, Z. Q.; Wong, G.; Dominguez, C.; de-Costa, B. R.; Rice, K. C.; Skolnick, P. Synthesis and evaluation of imidazo[1,5-α][1,4]-benzodiazepine esters with high affinities and selectivities at diazepam insensitive (DI) benzodiazepine receptors. J. Med. Chem. 1993, 36, 1001-1006.
19. Fryer, R. I.; Zhang, P.; Lin, K.-Y.; Upasani, R. B.; Wong, G.; Skolnick, P. Conformational similarity of diazepam-sensitive and -insensitive benzodiazepine receptors determined by chiral pyrroloimidazobenzodiazepines. Med. Chem. Res. 1993, 3, 183-191.
20. Wong, G.; Koehler, K. F.; Skolnick, P.; Gu, Z. Q.; Ananthan, S.; Schönholzer, P.; Hunkeler, W.; Zhang, W.; Cook, J. M. Synthetic and computer-assisted analysis of the structural requirements for selective, high affinity ligand binding to 'diazepam-insensitive' benzodiazepine receptors. J. Med. Chem. 1993, 36, 1820-1830.
21. A receptors. J. Med. Chem. 1995, 38, 1679-1688.
22. A-benzodiazepine receptors produced in transfected cells. Science 1989, 245, 1389-1392.
23. A/benzodiazepine receptors in a transfected cell line. Mol. Pharmacol. 1992, 42, 996-1003.
24. Skolnick, P.; Wong, G. Drug-receptor interactions in anxiety in imidazopyridines. In Anxiety disorders: a novel experimental and therapeutic approach; Bartholini, G., Garreau, M., Morselli, P., Zivkovic, B., Eds.; Raven Press: New York, 1993; pp 23-32.
25. 3H]flunitrazepam is histidine 102 of the alpha subunit. J. Biol. Chem. 1996, 271, 9209-9214.
26. 3H]Ro 15-4513. Neuropharmacology 1996, 35, 1199-1208.
27. Doble, A.; Martin, I. L. Multiple benzodiazepine receptors: no reason for anxiety. Trends Pharmacol. Sci. 1992, 13, 76-81.
28. Lippke, K. P.; Schunack, W. G.; Wenning, W.; Müller, W. E. β-Carbolines as benzodiazepine receptor ligands. 1. Synthesis and benzodiazepine receptor interaction of esters of β-carboline-3-carboxylic acid. J. Med. Chem. 1983, 26, 499-503.
29. Haefely, W.; Martin, J. R.; Schoch, P. Novel anxiolytics that act as partial agonists at benzodiazepine receptors. Trends Pharmacol. Sci. 1990, 11, 452-456.
30. Hagen, T. J.; Guzman, F.; Schultz, C.; Cook, J. M. Synthesis of 3,6-disubstituted β-carbolines which possess either benzodiazepine antagonist or agonist activity. Heterocycles 1986, 24, 2845-2855.
31. Allen, M. S.; Tan, Y. C.; Trudell, M. L.; Narayanan, K.; Schindler, L. R.; Martin, M. J.; Schultz, C.; Hagen, T. J.; Koehler, K. F.; Codding, P. W.; Skolnick, P.; Cook, J. M. Synthetic and computer-assisted analyses of the pharmacophore for the benzodiazepine receptor inverse agonist site. J. Med. Chem. 1990, 33, 2343-2357.
32. A receptors. J. Med. Chem. 1996, 39, 1928-1934.
33. Gee, K. W.; Brinton, R. E.; Yamamura, H. I. CL 218872 antagonism of diazepam induced loss of righting reflex: Evidence for partial agonistic activity at the benzodiazepine receptor. Life Sci. 1983, 32, 1037-1040.
34. Allen, M. S.; Hagen, T. J.; Trudell, M. L.; Codding, P. W.; Skolnick, P.; Cook, J. M. Synthesis of novel 3-substituted β-carbolines as benzodiazepine receptor ligands: probing the benzodiazepine receptor pharmacophore. J. Med. Chem. 1988, 31, 1854-1861.
35. Martin, M. J.; Trudell, M. L.; Diaz-Arauzo, H.; Allen, M. S.; Deng, L.; Schultz, C. A.; Tan, Y.-C.; Bi, Y.; Narayanan, K.; Dorn, L. J.; Koehler, K. F.; Skolnick, P.; Cook, J. M. Molecular yardsticks: rigid probes to define the spatial dimensions of the benzodiazepine receptor binding site. J. Med. Chem. 1992, 35, 4105-4117.
36. Trudell, M. L.; Lifer, S. L.; Tan, Y. C.; Martin, M. J.; Deng, L.; Skolnick, P.; Cook, J. M. Synthesis of substituted 7,12-dihydropyrido[3,2-b:5,4-b′]diindoles: rigid planar benzodiazepine receptor ligands with inverse agonist/antagonist properties. J. Med. Chem. 1990, 33, 2412-2420.
37. Trudell, M. L.; Basile, A. S.; Shannon, H. E.; Skolnick, P.; Cook, J. M. Synthesis of 7,12-dihydropyrido[3,4-b:5,4-b′]diindoles. A novel class of rigid, planar benzodiazepine receptor ligands. J. Med. Chem. 1987, 30, 456-458.
38. Arbilla, S., Depoortere, H.; George, P.; Langer, S. Z. Pharmacological profile of the imidazopyridine zolpidem at benzodiazepine receptors and electrocorticogram in rats. Naunyn-Schmiedebergs Arch. Pharmacol. 1985, 330, 248-251.
39. Yokoyama, N.; Ritter, B.; Neubert, A. D. 2-Arylpyrazolo[4,3-c]-quinolin-3-ones: novel agonist, partial agonist, and antagonist of benzodiazepines. J. Med. Chem. 1982, 25, 337-339.
40. Clements-Jewery, S.; Danswan, G.; Gardner, C. R.; Matharu, S. S.; Murdoch, R.; Tully, W. R.; Westwood, R. (Imidazo[1,2-a]-pyrimidin-2-yl)phenylmethanones and related compounds as potential nonsedative anxiolytics. J. Med. Chem. 1988, 31, 1220-1226.
41. Haefely, W.; Kyburz, E.; Gerecke, M.; Möhler, H. Recent advances in the molecular pharmacology of benzodiazepine receptors and in the structure-activity relationships of their agonists and antagonists. In Advances in Drug Research; Testa, B., Ed.; Academic Press: New York, 1985; pp 165-322.
42. Tarzia, G.; Occelli, E.; Toja, E.; Barone, D.; Corsico, N.; Gallico, L.; Luzzani, F. 6-(Alkylamino)-3-aryl-1,2,4-triazolo[3,4-a]phthalazines. A new class of benzodiazepine receptor ligands. J. Med. Chem. 1988, 31, 1115-1123.
43. A receptors. Mol. Pharmacol. 1992, 42, 294-301.
44. Allen, M. S.; LaLoggia, A. J.; Dorn, L. J.; Martin, M. J.; Costantino, G.; Hagen, T. J.; Koehler, K. F.; Skolnick, P.; Cook, J. M. Predictive binding of β-carboline inverse agonists and antagonists via the CoMFA/GOLPE approach. J. Med. Chem. 1992, 35, 4001-4010.
45. Braestrup, C.; Schmiechen, R.; Neff, G.; Nielsen, M. C.; Peterson, E. N. Interaction of convulsive ligands with benzodiazepine receptors. Science 1982, 216, 1241-1243.
46. Braestrup, C.; Honore, T.; Nielsen, M. C.; Peterson, E. N.; Jensen, L. H. Ligands for benzodiazepine receptors with positive and negative efficacy. Biochem. Pharmacol. 1984, 33, 859-862.
47. A receptor channels. In Ion Channels; Narahashi, T., Ed.; Plenum Press: New York, 1992; pp 315-343.
48. Barrett, J. E.; Brady, L. S.; Witkin, J. M.; Cook, J. M.; Larscheid, P. Interactions between the benzodiazepine receptor antagonist Ro 15-1788 (flumazenil) and the inverse agonist β-CCE: behavioral studies with squirrel monkeys. Life Sci. 1985, 36, 1407-1414.
49. Takada, K.; Winger, G.; Cook, J.; Larscheid, P.; Woods, J. H. Discriminative and aversive properties of β-carboline-3-carboxylic acid ethyl ester, a benzodiazepine receptor inverse agonist, in rhesus monkeys. Life Sci. 1986, 38, 1049-1056.
50. Shannon, H. E.; Hagen, T. J.; Guzman, F.; Cook, J. M. β-Carbolines as antagonists of the discriminative stimulus effects of diazepam in rats. J. Pharmacol. Exp. Ther. 1988, 246, 275-281.
51. A receptors. J. Med. Chem. 1998, 41, 2537-2552.
52. Zhang, W.; Koehler, K. F.; Zhang, P.; Cook, J. M. Development of a comprehensive pharmacophore model for the benzodiazepine receptor. Drug Des. Discov. 1995, 12, 193-248.
53. Zhang, W.; Diaz-Arauzo, H.; Allen, M. S.; Koehler, K. F.; Cook, J. M. Chemical and computer assisted development of the inclusive pharmacophore of benzodiazepine receptors. In Studies in Medicinal Chemistry; Choudhary, M. I., Ed.; Harwood Academic Publishers: New York, 1996; pp 303-373.
54. Villar, H. O.; Davies, M. F.; Loew, G. H.; Maguire, P. A. Molecular models for recognition and activation at the benzodiazepine receptor: a review. Life Sci. 1991, 48, 593-602.
55. Villar, H. O.; Uyeno, E. T.; Toll, L.; Polgar, W.; Davies, M. F.; Loew, G. H. Molecular determinants of benzodiazepine receptor affinities and anticonvulsant activities. Mol. Pharmacol. 1989, 36, 589-600.
56. Crippen, G. M. Distance geometry analysis of the benzodiazepine binding site. Mol. Pharmacol. 1981, 22, 11-19.
57. Ghose, A. K.; Crippen, G. M. Modeling the benzodiazepine receptor binding site by the general three-dimensional structure-directed quantitative structure-activity relationship method REMOTEDISC. Mol. Pharmacol. 1990, 37, 725-734.
58. Codding, P. W.; Muir, A. K. S. Molecular structure of Ro 15-1788 and a model for the binding of benzodiazepine receptor ligands. Mol. Pharmacol. 1985, 28, 178-184.
59. Muir, A. K. S.; Codding, P. W. Structure-activity studies of β-carbolines. 3. Crystal and molecular structures of methyl β-carboline-3-carboxylate. Can. J. Chem. 1985, 63, 2752-2756.
60. Fryer, R. I. Ligand interactions at the benzodiazepine receptor. In Comprehensive Medicinal Chemistry; Emmett, J., Ed.; Pergamon Press: Oxford, U.K., 1989; pp 539-566.
61. Borea, P. A.; Gilli, G.; Bertolasi, V.; Ferretti, V. Stereochemical features controlling binding and intrinsic activity properties of benzodiazepine-receptor ligands. Mol. Pharmacol. 1987, 31, 334-344.
62. Tebib, S.; Bourguignon, J. J.; Wermuth, C. G. The active analogue approach applied to the pharmacophore identification of benzodiazepine receptor ligands. J. Comput.-Aided Mol. Des. 1987, 1, 153-170.
63. Gardner, C. R. A review of recently developed ligands for neuronal benzodiazepine receptors and their pharmacological activities. Prog. Neuro-Psychopharmacol. Biol. Psychiat. 1992, 16, 755-781.
64. Codding, M. G.; Roszak, A. W.; Szkaradzinska, M. B.; Cook, J. M.; Aha, L. J. Modeling the benzodiazepine receptor using structural and theoretical characterization of novel β-carbolines. In Trends in Medicinal Chemistry'88; van der Goot, H., Domány, G., Pallos, L., Timmerman, H., Eds.; Elsevier Science Publishers: Amsterdam, 1989; pp 109-120.
65. Naryanan, K.; Cook, J. M. Molecular yardsticks: synthesis of higher homologues of 7,12-dihyropyrido[3,4-b:5,4-b′]diindole. Probing the dimensions of the benzodiazepine receptor inverse agonist site. Heterocycles 1990, 31, 203-208.
66. Hollinshead, S. P.; Trudell, M. L.; Skolnick, P.; Cook, J. M. Structural requirements for agonist actions at the benzodiazepine receptor: studies with analogues of 6-(benzyloxy)-4-(methoxymethyl)-β-carboline-3-carboxylic acid ethyl ester. J. Med. Chem. 1990, 33, 1062-1069.
67. Diaz-Arauzo, H.; Evoniuk, G. E.; Skolnick, P.; Cook, J. M. The agonist pharmacophore of the benzodiazepine receptor. Synthesis of a selective anticonvulsant/anxiolytic. J. Med. Chem. 1991, 34, 1754-1756.
68. Cook, J. M.; Diaz-Arauzo, H.; Allen, M. S. Inverse agonists: probes to study the structure, topology and function of the benzodiazepine receptor. Natl. Inst. Drug Abuse Res. Monogr. 1991, 133-139.
69. Diaz-Arauzo, H.; Koehler, K. F.; Hagen, T. J.; Cook, J. M. Synthetic and computer assisted analysis of the pharmacophore for agonists at benzodiazepine receptors. Life Sci. 1991, 49, 207-216.
70. Zhang, W.; Koehler, K. F.; Harris, B.; Skolnick, P.; Cook, J. M. The synthesis of benzofused benzodiazepines employed as probes of the agonist pharmacophore of benzodiazepine receptors. J. Med. Chem. 1994, 37, 745-757.
71. A/benzadiazepine receptor subsites. Potent affinities of the (S)-enantiomers of framework-constrained 4,5-substituted pyrroloimidazobenzodiazepines. Med. Chem. Res. 1997, 7, 25-35.
72. Huang, Q.; Zhang, W.; Liu, R.; McKernan, R. M.; Cook, J. M. Benzo-fused benzodiazepines employed as topological probes for the study of benzodiazepine receptor subtypes. Med. Chem. Res. 1996, 6, 384-391.
73. A/BzR subtypes [αxβ3γ2 (x = 1-3, 5 and 6)] via CoMFA. J. Med. Chem. 1998, 41, 4230-4142.
74. A/benzodiazepine receptor subtypes: Binding affinities of substituted β-carboline ligands for αxβ3γ2 (x = 1-3, 5, 6) subtypes and quantitative structure-activity relationship studies via comparative molecular field analysis. Drug Des. Discov. 1999, 16, 55-76.
75. A/BzR receptor subtypes. Part I. Evidence for the conservation of pharmacophoric descriptors for DS subtypes. Med. Chem. Res. 1999, 9, 186-202.
76. Ligands related to loprazolam are not included because subtype selectivity data was not available.
77. A/benzodiazepine receptor subtype. Med. Chem. Res. 1995, 5, 700-709.
78. 2. Acta Crystallogr., Sect. C: Cryst. Struct. Commun. 1984, 40, 1981-1983.
79. Camerman, A.; Camerman, N. Stereochemical basis of anticonvulsant drug action. II. Molecular structure of diazepam. J. Am. Chem. Soc. 1972, 94, 268-272.
80. 3O. Acta Crystallogr., Sect. C: Cryst. Struct. Commun. 1985, C41, 107-110.
81. Hempel, A.; Camerman, N.; Camerman, A. Benzodiazepine stereochemistry: Crystal structures of the diazepam antagonist Ro 15-1788 and the anomalous benzodiazepine Ro 5-4864. Can. J. Chem. 1987, 65, 1608-1612.
82. Neidle, S.; Webster, G. D.; Jones, G. B.; Thurston, D. E. Structures of two DNA minor-groove binders based on pyrrolo[2,1-c][1,4]-benzodiazepines. Acta Crystallogr. 1991, C47, 2678-2680.
83. Halgren, T. A. Merck molecular force field. I. Basis, form, scope, parametrization, and performance of MMFF94. J. Comput. Chem. 1996, 17, 490-519.
84. Halgren, T. A. Merck molecular force field. II. MMFF94 van der Waals and electrostatic parameters for intermolecular interactions. J. Comput. Chem. 1996, 17, 520-552.
85. Halgren, T. A. Merck molecular force field. III. Molecular geometrics and vibrational frequencies for MMFF94. J. Comput. Chem. 1996, 17, 553-586.
86. Halgren, T. A.; Nachbar, R. B. Merck molecular force field. IV. Conformational energies and geometries for MMFF94. J. Comput. Chem. 1996, 17, 587-615.
87. Halgren, T. A. Merck molecular force field. V. Extension of MMFF94 using experimental data, additional computational data, and empirical rules. J. Comput. Chem. 1996, 17, 616-641.
88. Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W. C. Macro-Model-An integrated software system for modeling organic and bioorganic molecules using molecular mechanics. J. Comput. Chem. 1990, 11, 440-467.
89. Gaussian92, Gaussian, Inc., Carnegie Office Park, Bldg. 6, Pittsburgh, PA 15106.
90. Gaussian94, Gaussian, Inc., Carnegie Office Park, Bldg. 6, Pittsburgh, PA 15106.
91. Andzelm, J.; Klobukowski, M.; Radzio-Andzelm, E. Compact contracted Gaussian-type basis sets for halogen atoms. Basis-set superposition effects on molecular properties. J. Comput. Chem. 1984, 5, 146-161.
92. The M4 basis set for Br and I, which is then split to obtain the 6-31G quality basis set (SV4) and d functions are added to obtain the 6-31G* basis set, also referred to as the SV4P basis sets. Personal communication with Dr. Misra Ashutosh.
93. McGrath, M. P.; Radom, L. Extension of Gaussian-1 (G1) theory to bromine-containing molecules. J. Chem.Phys. 1991, 94, 511-516.
94. Glukhovtsev, M. N.; Pross, A.; McGrath, M. P.; Radom, L. Extension of Gaussian-2 (G2) theory to bromine- and iodine-containing molecules: Use of effective core potentials. J. Chem. Phys. 1995, 103, 1878-1885.
95. Glukhovtsev, M. N.; Pross, A.; McGrath, M. P.; Radom, L. Erratum: Extension of Gaussian-2 (G2) theory to bromine- and iodine-containing molecules: Use of effective core potentials. J. Chem. Phys. 1996, 104, 3407.
96. 1) subtype. J. Pharmacol. Exp. Ther. 1988, 245, 1033-1041.
97. A receptor subtypes. Mol. Pharmacol. 1993, 43, 240-244.
98. SYBYL6.4, Tripos, Inc., 1699 S. Hanley Rd., St. Louis, MO 63144-2913.
99. Boobbyer, D. N.; Goodford, P. J.; McWhinnie, P. M.; Wade, R. C. New hydrogen-bond potentials for use in determining energetically favorable binding sites on molecules of known structure. J. Med. Chem. 1989, 32, 1083-1094.
100. Ippolito, J. A.; Alexander, R. S.; Christianson, D. W. Hydrogen bond stereochemistry in protein structure and function. J. Mol. Biol. 1990, 215, 457-471.
101. Murray-Rust, P.; Glusker, J. P. Directional hydrogen bonding to sp2 and sp3-hybridized oxygen atoms and its relevance to ligand-macromolecular interactions. J. Am. Chem. Soc. 1984, 106, 1018-1025.
102. Tintelnot, M.; Andrews, P. Geometries of functional group interactions in enzyme-ligand complexes: guides for receptor modelling. J. Comput.-Aided Mol. Des. 1989, 3, 67-84.
103. Vedani, A.; Huhta, D. W. A new force field for modeling metalloproteins. J. Am. Chem. Soc. 1991, 113, 5860-5862.
104. A receptors containing α5 subunits. J. Pharmacol. Exp. Ther. 1997, 283, 488-495.
105. A/BzR sites. Med. Chem. Res. 1999, 9, 71-88.
106. 3H]3-carboethoxy-β-carboline binding by irazepine: evidence for multiple "domains" of the benzodiazepine receptor. J. Neurochem. 1982, 39, 1142-1146.
107. 3H]Ro 15-4513 binding in intact cultured cerebellar granule cells. Eur. J. Pharmacol. 1989, 169, 53-60.
108. Wong, C.-G.; Langer, T.; Kamath, P. G.; Gu, Z.-Q.; Skonick, P.; Fryer, R. I. Computer-aided molecular modeling, synthesis, and biological evaluation of 8-(benzyloxy)-2-phenylpyrazolo[4,3-c]-quinoline as a novel benzodiazepine receptor agonist ligand. J. Med. Chem. 1995, 38, 950-957.
109. Zhang, W. Ph.D. Thesis. Part I: Chemical and Computer Assisted Development of an Inclusive Pharmacophore for the Benzodiazepine Receptor. Studies Directed Toward the Synthesis of Anxioselective Anxiolytics. Part II: Molecular Yardsticks: Probes to study the Actual Dimensions of Benzodiazepine Receptors. University of Wisconsin-Milwaukee, 1994.
110. 3H-diazepam displacing activity from human urine. Life Sci. 1979, 25, 679-686.
111. Schweri, M.; Cain, M.; Cook, J.; Paul, S.; Skolnick, P. Blockade of 3-carbomethoxy-β-carboline induced seizures by diazepam and the benzodiazepine antagonists, Ro 15-1788 and CGS 8216. Pharmacol. Biochem. Behav. 1982, 17, 457-460.
112. Cain, M.; Weber, R. W.; Guzman, F.; Cook, J. M.; Barker, S. A.; Rice, K. C.; Crawley, J. N.; Paul, S. M.; Skolnick, P. β-Carbolines: synthesis and neurochemical and pharmacological actions on brain benzodiazepine receptors. J. Med. Chem. 1982, 25, 1081-1091.
113. Fryer, R. I.; Cook, C.; Gilman, N. W.; Walser, A. Conformational shifts at the benzodiazepine receptor related to the binding of agonists, antagonists, and inverse agonists. Life Sci. 1986, 39, 1947-1957.
114. Hagen, T. J.; Skolnick, P.; Cook, J. M. Synthesis of 6-substituted β-carbolines that behave as benzodiazepine receptor antagonists or inverse agonists. J. Med. Chem. 1987, 30, 750-753.
115. Trullas, R.; Ginter, H.; Jackson, B.; Skolnick, P.; Allen, M. S.; Hagen, T. J.; Cook, J. M. 3-Ethoxy-β-carboline: a high affinity benzodiazepine receptor ligand with partial inverse agonist properties. Life Sci. 1988, 43, 1193-1197.
116. Petersen, E. N.; Jensen, L. H.; Honore, T.; Braestrup, C. Differential pharmacological effects of benzodiazepine receptor inverse agonists. Adv. Biochem. Psychopharmacol. 1983, 38, 57-64.
117. Jensen, L. H.; Petersen, E. N. Bidirectional effects of benzodiazepine receptor ligands against picrotoxin- and pentylenetetrazol-induced seizures. J. Neural Transm. 1983, 58, 183-191.
118. Nielsen, M. C.; Braestrup, C. Ethyl β-carboline-3-carboxylate shows differential benzodiazepine receptor interaction. Nature 1980, 286, 606-607.
119. 3H]-methyl β-carboline-3-carboxylate to brain benzodiazepine receptors. Nature 1981, 294, 472-474.
120. A receptors by benzodiazepine receptor ligands. In Allosteric Modulation of Amino Acid Receptors: Therapeutic Implications.; Barnard, E. A., Costa, E., Eds.; Raven Press: New York, 1989; pp 47-70.
121. Stephens, D. N.; Schneider, H. H.; Kehr, W.; Andrews, J. S.; Rettig, K. J.; Turski, L.; Schmiechen, R.; Turner, J., D.; Jensen, L. H.; Petersen, E. N.; Honore, T.; Bondo-Hansen, J. Abecarnil, a metabolically stable, anxioselective β-carboline acting at benzodiazeoine receptors. J. Pharmacol. Exp. Ther. 1990, 334-343.
122. 1 receptor subtype specific antagonist. Med. Chem. Res. 1995, 5, 710-718.
123. Personal communication with Dr. Harry June.
124. A/benzodiazepine receptors. Med. Chem. Res. 1992, 2, 217-224.
125. Fryer, R. I.; Zhang, P.; Rios, R.; Gu, Z. Q.; Basile, A. S.; Skolnick, P. Structure-activity relationship studies at benzodiazepine receptors (BzR): a comparison of the substituent effects of pyrazoloquinolinone analogues. J. Med. Chem. 1993, 36, 1669-1673.
126. Takada, S.; Shindo, H.; Sasatani, T.; Chomei, N.; Matsushita, A.; Eigyo, M.; Kawasaki, K.; Murata, S.; Takahara, Y.; Shintaku, H. Thienylpyrazoloquinolines: potent agonists and inverse agonists to benzodiazepine receptors. J. Med. Chem. 1988, 31, 1738-1745.
127. Allen, M. S.; Skolnick, P.; Cook, J. M. Synthesis of novel phenyl-2H-pyrazolo[4,3-c]isoquinolin-3-ols: topological comparisons with analogues of 2-phenyl-2,5-dihydropyrazolo[4,3-c]quinolin-3(3H)-ones at benzodiazepine receptors. J. Med. Chem. 1992, 35, 368-374.
128. Huang, Q. Ph.D. Thesis, University of Wisconsin-Milwaukee, 1998.
129. A/ BzR subtypes: binding affinities of symmetrically substituted pyrazolo[4,3-c]quinolin-3-ones at recombinant αxβ3γ2 subtypes and quantitative structure-activity relationsbip studies via a comparative molecular field analysis. Drug Des. Discov. 1999, 16, 77-91.
130. Braestrup, C.; Nielsen, M. C.; Olsen, C. E. Urinary and brain β-carboline-3-carboxylates as potent inhibitors of brain benzodiazepine receptors. Proc. Natl. Acad. Sci. U.S.A. 1980, 77, 2288-2292.
131. Haefely, W. E.; Kulcsar, A.; Möhler, H.; Pieri, L.; Polc, P.; Schaffner, R. Possible involvement of GABA in the central actions of benzodiazepines. In Advances in Biochemical Psychopharmacology; Costa, E., Greengard, P., Eds.; Raven Press: New York, 1975; pp 131-151.
132. Squires, R. GABA and Benzodiazepine Receptors; CRC Press: Boca Raton, FL, 1988.
133. A Receptors. Neuropsychopharmacology 1999, 20, 255-262.
134. Sanger, D. J.; Benavides, J.; Perrault, G.; Morel, E.; Cohen, C.; Joly, D.; Zivkovic, B. Recent developments in the behavioral pharmacology of benzodiazepine (ω) receptors: Evidence for the functional significance of receptor subtypes. Neurosci. Biobehav. Rev. 1994, 18, 1.
135. Zhang, W.; Liu, R.; Huang, Q.; Zhang, P.; Koehler, K.; Harris, B.; Skolnick, P.; Cook, J. M. Synthesis of 5-thienyl and 5-furyl substituted benzodiazepines: Probes of the pharmacophore for benzodiazepine receptor agonists. Eur. J. Med. Chem. 1995, 30, 483-496.
136. Lippa, A. S.; Coupet, J.; Greenblatt, E. N.; Klepner, C. A.; Beer, B. A synthetic nonbenzodiazepine ligand for benzodiazepine receptors: A probe for investigating neuronal substrates of anxiety. Pharmacol. Biochem. Behav. 1979, 11, 99-106.
137. A receptor is dependent on the type of gamma-subunit present. J. Recept. Signal Transduct. Res. 1995, 15, 173-183.
138. Villiger, J. W.; Taylor, K. M.; Gluckman, P. D. Characteristics of type 1 and type 2 benzodiazepine receptors in the bovine brain. Pharmacol. Biochem. Behav. 1982, 16, 373-375.
139. Langer, S. Z.; Arbilla, S. Imidazopyridines as a tool for the characterization of benzodiazepine receptors: A proposal for a pharmacological classification as omega receptor subtypes. Pharmacol. Biochem. Behav. 1988, 29, 763-766.
140. Private communication with Dr. Mireille Sevrin of Synthélabo, National ACS Meeting, Dallas, TX, spring of 1998.
141. A/benzodiazepine receptor on Pavlovian conditioning. Submitted.
142. A-benzodiazepine receptors in the striatum are involved in the sedation produced by a moderate, but not an intoxicating ethanol dose in outbred Wistar rats. Brain Res. 1998, 794, 103-118.
143. Suzdak, P. D.; Glowa, J. R.; Crawley, J. N.; Schwartz, R. D.; Skolnick, P.; Paul, S. M. A selective imidazobenzodiazepine antagonist of ethanol in the rat. Science 1986, 234, 1243-1247.
144. Draski, L. J.; Deitrich, R. A. Initial effects of ethanol on the central nervous system. In Pharmacological Effects of Ethanol on the Nervous System; Deitrich, R. A., Erwin, V. G., Eds.; CRC Press: Boca Raton, FL, 1996; pp 277-294.
145. Jackson, H. C.; Nutt, D. J. Inverse agonists and alcohol. In Benzodiazepine Receptor Inverse Agonists; Sarter, M., Nutt, D. J., Lister, R. G., Eds.; Wiley-Liss: New York, 1995; pp 113-138.
146. June, H. L.; Duemler, S. E.; Greene, T. L.; Williams, J. A.; Lin, M.; Devaraju, S. H. A.; Lewis, M. J.; Murphy, J. M. Effects of benzodiazepine inverse agonist Ro19-4603 on the maintenance of tolerance to a single dose of ethanol. J. Pharmacol. Exp. Ther. 1995, 274, 1105-1112.
147. Liu, R. Ph.D. Thesis, University of Wisconsin-Milwaukee, 1996.
148. Koob, G. F. Drug abuse: anatomy, pharmacology and function of reward pathways. Trends Pharmacol. Sci. 1992, 13, 177-184.
149. A receptor subunit mRNAs in the rat brain. I. telencephalon, diencephalon, mesencephalon. J. Neurosci. 1992, 12, 1040-1062.
150. Overton, D. A. Major theories of state dependent learning. In Drug Discrimination and State Dependent Learning; Ho, B. T., Richards III, D. W., Chute, D. L., Eds.; Academic Press: New York, 1978; pp 283-318.
151. Cole, B. J.; Hillmann, M. Effects of benzodiazepine receptor ligands on the performance of an operant delayed matching to position task in rats: Opposite effects of FG 7142 and lorazepam. Psychopharmacology (Berlin) 1994, 115, 350-357.
152. Britton, K. T.; Ehlers, C. L.; Koob, G. F. Is ethanol antagonist Ro 15-4513 selective for ethanol? Science 1988, 239, 648-649.
153. Forster, M. J.; Prather, P. L.; S. R., P.; Lal, H. The benzodiazepine receptor inverse agonist Ro 15-3505 reverses recent memory deficits in aged mice. Pharmacol. Biochem. Behav. 1995, 51, 557-560.
154. Anglade, F.; Bizot, J. C.; Dodd, R. H.; Baudoin, C.; Chapouthier, G. Opposite effects of cholinergic agents and benzodiazepine receptor ligands in a passive avoidance task in rats. Neurosci. Lett. 1994, 182, 247-250.
155. Yasui, M.; Kawasaki, K.; Matsushita, A.; Satoh, M. Benzodiazepine inverse agonists augment long-term potentiation in CA1 and CA3 of guinea pig hippocampal
156. Mello, N. K. The effect of alcohol on short-term memory in rhesus monkeys. Psychopharm. Bull. 1971, 8, 20-22.
157. Roberts, W. A.; Grant, D. S. Studies of short-term memory in the pigeon using the delayed matching to sample procedure. In Processes of Animal Memory; Medlin, D. L., Roberts, W. A., Davis, R. T., Eds.; Lawrence Earlbaum Associates: New York, 1976; pp 79-112.
158. Pontecorvo, M. J.; Clissold, D. B.; Conti, L. H. Aged-related cognitive impairments as assessed with an automated repeated measures memory task: Implication for the possible role of acetylcholine and norepinephrine in memory dysfunction. Neurobiol. Aging 1988, 9, 617-625.
159. Glick, S. D.; Jarvik, M. E. Impairment by d-amphetamine of delayed matching performance in monkeys. J. Pharmacol. Exp. Ther. 1969, 169, 1-6.
160. Schulze, G. E.; Slikker, W. J.; Paule, M. G. Multiple behavioral effects of diazepam in rhesus monkeys. Pharmacol. Biochem. Behav. 1989, 34, 29-35.
161. Wenger, G. R.; Wright, D. W. Disruption of performance under a titrating matching-to-sample schedule of reinforcement by drugs of abuse. J. Pharmacol. Exp. Ther. 1990, 254, 258-269.
162. Roche, J. D.; Cherek, D. R.; Spiga, R.; Bennett, R. H.; Cowan, K. A.; Yingling, J. Benzodiazepine-induced impairment of matching-to-sample performance in humans. Pharmacol. Biochem. Behav. 1990, 36, 945-952.
163. Hudzik, T. J.; Wenger, G. R. Effects of drugs of abuse and cholinergic agents on delayed matching-to-sample responding in the squirrel monkey. J. Pharmacol. Exp. Ther. 1994, 265, 120-127.
164. Hake, D. F.; Azrin, N. H. An apparatus for delivering pain shock to monkeys. J. Exp. Anal. Behav. 1963, 6, 297-298.
165. Azrin, N. H. A technique for delivering shock to pigeons. J. Exp. Anal. Behav. 1959, 2, 161-163.
166. McMillan, D. E. Effects of chemicals on delayed matching behavior in pigeons. II Tolerance to the effects of diazepam and cross tolerance to phencyclidine. Neurotoxicology 1982, 3, 138-141.
167. Pontecorvo, M. J.; Clissold, D. B.; White, M. F.; Ferkany, J. W. N-Methyl-D-aspartate antagonists and working memory performance: Comparison with the effects of scopolamine, propranolol, diazepam and phenylisopropyladenosine. Behav. Neurosci. 1991, 105, 521-535.
168. Wenger, G. R.; Hudzik, T. J.; Wright, D. W. Titrating matching-to-sample performance in pigeons: Effects of diazepam, morphine, and cholinergic agents. Pharmacol. Biochem. Behav. 1993, 46, 435-443.
169. Stein, L.; Wise, C. D.; Berger, B. D. Antianxiety action of benzodiazepines: Decrease in activity of serotonin neurons in the punishment system. In The Benzodiazepines; Garattini, S., Mussini, E., Randall, L. O., Eds.; Raven Press: New York, 1973; pp 299-326.
170. McMillan, D. E. Effects of drug on behavior before and during chronic diazepam administration. Eur. J. Pharmacol. 1992, 215, 145-152.
171. McMillan, D. E.; Li, M.; Hardwick, W. C. Discriminative stimulus effects and antipunishment effects of drugs measured during the same session. Pharmacol. Biochem. Behav. 1997, 56, 161-166.
172. Shumsky, J. S.; Lucki, I. Differential tolerance to the effects of chlordiazepoxide on unpunished and punished operant responding following chronic treatment. Pharmacol. Biochem. Behav. 1996, 53, 593-601.
173. A receptor subtypes in adult rat hippocampus and cerebellum. Neuroscience 1996, 73, 697-704.
174. File, S. E.; Dingemanse, J.; Friedman, H. I.; Greenblatt, D. J. Chronic treatment with Ro 15-1788 distinguishes between its benzodiazepine antagonist, agonist and inverse agonist properties. Psychopharmacology (Berlin) 1986, 89, 113-117.
175. Another possible reason is that there are several obvious differences between Helmstetter's studies and our studies including: species (pigeon and squirrel monkey vs rat), differences in the light:dark cycle (12:12 vs 14:10), route of injection (im vs hipppocampal), Pavlovian vs operant conditioning, and food-maintained responding vs aversive stimulus-produced freeing. There also is the issue of acquisition/learning and 24-h recall vs our matching-to-sample procedure which is usually considered a measure of working or short-term memory. In addition, local differences in concentration of drug in the hippocampus (systemic vs intrahippocampal) may be drastically different depending on peripheral metabolism. Active metabolites might also be generated and further complicated the issue. More work in this area will be required to exclude these possibilities.
176. Cox, E. Ph.D. Thesis, University of Wisconsin-Milwaukee, 1997.
177. Hadingham, K. L.; Wingrove, P. B.; Wafford, K. A.; Bain, C.; Kemp, J. A.; Palmer, K. J.; Wilson, A. W.; Wilcox, A. S.; Sikela, J. M.; Ragan, C. I.; Whiting, P. J. Role of the β subunit in determining the pharmacology of human γ-aminobutyric acid type A receptors. Mol. Pharmacol. 1993, 44, 1211-1218.