Enantiomeric propanolamines as selective N-methyl-D-aspartate 2B receptor antagonists

Journal of Medicinal Chemistry

Volumn 51, Issue 18, 2008, Pages 5506-5521

  Tahirovic, Yesim A ^a   Geballe, Matthew ^a   Gruszecka Kowalik, Ewa ^d   Myers, Scott J ^b   Lyuboslavsky, Polina ^b   Le, Phuong ^b   French, Adam ^b   Irier, Hasan ^b   Choi, Woo Baeg ^d   Easterling, Keith ^b   Yuan, Hongjie ^b   Wilson, Lawrence J ^a   Kotloski, Robert ^c   McNamara, James O ^c   Dingledine, Raymond ^b   Liotta, Dennis C ^a   Traynelis, Stephen F ^b   Snyder, James P ^a  

^a EMORY UNIVERSITY   (United States)

^b EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d GEORGIA INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (4 METHANESULFONAMIDOPHENOXY) 3 (3,4 DICHLOROPHENYLETHYLAMINO) 2 PROPANOL DERIVATIVE; 1 (4 METHANESULFONAMIDOPHENOXY) 3 (N ETHYL 3,4 DICHLOROPHENYLETHYLAMINO) 2 PROPANOL DERIVATIVE; AMINE; AMINE NITROGEN; BENZIMIDAZOLE DERIVATIVE; BENZYL CINNAMAMIDINE DERIVATIVE; BESONPRODIL; CINNAMAMIDE DERIVATIVE; ELIPRODIL; HALOPERIDOL; IFENPRODIL; INDOLE 2 CARBOXAMIDE DERIVATIVE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 2B ANTAGONIST; NITROGEN; OXAMIDE DERIVATIVE; PROPANOLAMINE DERIVATIVE; RO 256981; TRAXOPRODIL; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTICONVULSANT ACTIVITY; ARTICLE; C57BL 6 MOUSE; CELL DEATH; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG HALF LIFE; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG RECEPTOR BINDING; DRUG STRUCTURE; ENANTIOMER; ENANTIOSELECTIVITY; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; IN VIVO STUDY; ISCHEMIA; LOCOMOTION; MOUSE; NEUROPROTECTION; NONHUMAN; RAT; RODENT; SPRAGUE DAWLEY RAT; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION;

ANIMALS; ANTICONVULSANTS; BLOOD-BRAIN BARRIER; BRAIN; EXCITATORY AMINO ACID ANTAGONISTS; MAGNETIC RESONANCE SPECTROSCOPY; MASS SPECTROMETRY; MOTOR ACTIVITY; PROPANOLAMINES; RATS; RECEPTORS, N-METHYL-D-ASPARTATE; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; XENOPUS;

EID: 52449094728     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm8002153     Document Type: Article

References (79)

1. Dingledine, R.; Borges, K.; Bowie, D.; Traynelis, S. F. The glutamate receptor ion channels. Pharmacol. Rev. 1999, 51, 7-61.
2. Erreger, K.; Chen, P.; Wyllie, D. J. A.; SF, T. Glutamate receptor gating. Crit. Rev. Neurobiol. 2004, 16, 187-224.
3. Kew, J. N. C.; Kemp, J. A. Ionotropic and metabotropic glutamate receptor structure and pharmacology. Psychopharmacology 2005, 179, 4-29.
4. Chenard, B. L.; Menniti, F. S. Antagonists selective for NMDA receptors containing the NR2B subunit. Curr. Pharm. Des. 1999, 5, 381-404.
5. Chazot, P. L. The NMDA receptor NR2B subunit: a valid therapeutic target for multiple CNS pathologies. Curr. Med. Chem. 2004, 11, 389-396.
6. Wang, C.; Shuaib, A. NMDA/NR2B selective antagonists in the treatment of ischemic brain injury. Curr. Drug Targets CNS Neurol. Disord. 2005, 4, 143-151.
7. Layton, M. E.; Kelly, M. J.; Rodzinak, K. J. Recent advances in the development of NR2B subtype-selective NMDA receptor antagonists. Curr. Top. Med. Chem. 2006, 6, 697-709.
8. Moriyoshi, K.; Masu, M.; Ishii, T.; Shigemoto, R.; Mizuno, N.; Nakanishi, S. Molecular-Cloning and Characterization of the Rat NMDA Receptor. Nature 1991, 354, 31-37.
9. Sugihara, H.; Moriyoshi, K.; Ishii, T.; Masu, M.; Nakanishi, S. Structures and Properties of 7 Isoforms of the NMDA Receptor Generated by Alternative Splicing. Biochem. Biophys. Res. Commun. 1992, 185, 826-832.
10. Monyer, H.; Sprengel, R.; Schoepfer, R.; Herb, A.; Higuchi, M.; Lomeli, H.; Burnashev, N.; Sakmann, B.; Seeburg, P. H. Heteromeric NMDA Receptors: Molecular and Functional Distinction of Subtypes. Science 1992, 256, 1217-1221.
11. Monyer, H.; Burnashev, N.; Laurie, D. J.; Sakmann, B.; Seeburg, P. H. Developmental and Regional Expression in the Rat-Brain and Functional Properties of 4 NMDA Receptors. Neuron 1994, 12, 529-540.
12. 2+ inhibition of the NMDA receptor. Neuron 1999, 23, 171-180.
13. Low, C. M.; Zheng, F.; Lyuboslavsky, P.; Traynelis, S. F. Molecular determinants of coordinated proton and zinc inhibition of N-methyl- D-aspartate NR1/NR2A receptors. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 11062-11067.
14. Paoletti, P.P.-D., F.; Fayyazuddin, A.; Le Goff, A.; Callebaut, I.; Neyton, J. Molecular organization of zinc binding N-terminal modulatory domain in a NMDA receptor subunit. Neuron 2000, 28, 911-925.
15. Perin-Dureau, F.; Rachline, J.; Neyton, J.; Paoletti, P. Mapping the binding site of the neuroprotectant ifenprodil on NMDA receptors. J. Neurosci. 2002, 22, 5955-5965.
16. Williams, K. Ifenprodil Discriminates Subtypes of the N-Methyl-D-Aspartate Receptor: Selectivity and Mechanisms at Recombinant Heteromeric Receptors. Mol. Pharmacol. 1993, 44, 851-859.
17. Scatton, B.; Avenet, P.; Benavides, J.; Carter, C.; Duverger, D.; Oblin, A.; Perrault, G.; Sanger, D. J.; Schoemaker, H. Neuroprotective Potential of the Polyamine site-directed NMDA Receptor Antagonists: Ifenprodil and Eliprodil. In Direct and Allosteric Control of Glutamate Receptors; Palfreyman, M. G., Reynolds, I. J., Skolnick, P., Eds.; CRC Press: Boca Raton, FL, 1994; p 139.
18. Chenard, B. L.; Bordner, J.; Butler, T. W.; Chambers, L. K.; Collins, M. A.; Decosta, D. L.; Ducat, M. F.; Dumont, M. L.; Fox, C. B.; Mena, E. E.; Menniti, F. S.; Nielsen, J.; Pagnozzi, M. J.; Richter, K. E. G.; Ronau, R. T.; Shalaby, I. A.; Stemple, J. Z.; White, W. F. (1S,2S)-1-(4- Hydroxyphenyl)-2-(4-Hydroxy-4-Phenylpiperidino)-1-Propanol: A Potent New Neuroprotectant Which Blocks N-Methyl-D-Aspartate Responses. J. Med. Chem. 1995, 38, 3138-3145.
19. Mott, D. D.; Doherty, J. J.; Zhang, S. N.; Washburn, M. S.; Fendley, M. J.; Lyuboslavsky, P.; Traynelis, S. F.; Dingledine, R. Phenylethanolamines inhibit NMDA receptors by enhancing proton inhibition. Nat. Neurosci. 1998, 1, 659-667.
20. Fischer, G.; Mutel, V.; Trube, G.; Malherbe, P.; Kew, J. N. C.; Mohacsi, E.; Heitz, M. P.; Kemp, J. A. Ro 25-6981, a highly potent and selective blocker of N-methyl-D-aspartate receptors containing the NR2B subunit. Characterization in vitro. J. Pharmacol. Exp. Ther. 1997, 283, 1285-1292.
21. Barta-Szalai, G.; Borza, I.; Bozo, E.; Kiss, C.; Agai, B.; Proszenyak, A.; Keseru, G. M.; Gere, A.; Kolok, S.; Galgoczy, K.; Horvath, C.; Farkas, S.; Domany, G. Oxamides as novel NR2B selective NMDA receptor antagonists. Bioorg. Med. Chem. Lett. 2004, 14, 3953-3956.
22. McCauley, J. A.; Theberge, C. R.; Romano, J. J.; Billings, S. B.; Anderson, K. D.; Claremon, D. A.; Freidinger, R. M.; Bednar, R. A.; Mosser, S. D.; Gaul, S. L.; Connolly, T. M.; Condra, C. L.; Xia, M. H.; Cunningham, M. E.; Bednar, B.; Stump, G. L.; Lynch, J. J.; Macaulay, A.; Wafford, K. A.; Koblan, K. S.; Liverton, N. J. NR2B-selective N-methyl-D-aspartate antagonists: synthesis and evaluation of 5-substituted benzimidazoles. J. Med. Chem. 2004, 47, 2089-2096.
23. Borza, I.; Kolok, S.; Gere, A.; Agai-Csongor, E.; Agai, B.; Tarkanyi, G.; Horvath, C.; Barta-Szalai, G.; Bozo, E.; Kiss, C.; Bielik, A.; Nagy, J.; Farkas, S.; Domany, G. Indole-2-carboxamides as novel NR2B selective NMDA receptor antagonists. Bioorg. Med. Chem. Lett. 2003, 13, 3859-3861.
24. Curtis, N. R.; Diggle, H. J.; Kulagowski, J. J.; London, C.; Grimwood, S.; Hutson, P. H.; Murray, F.; Richards, P.; Macaulay, A.; Wafford, K. A. Novel N-1-(benzyl)cinnamamidine derived NR2B subtype-selective NMDA receptor antagonists. Bioorg. Med. Chem. Lett. 2003, 13, 693-696.
25. Wright, J. L.; Kesten, S. R.; Upasani, R. B. LanN. C. 4-Benzylpiperidinylalkylsulfinyl-substituted heterocycles and their use as subtype-selective NMDA receptor antagonists. WO 2000000197, 2000.
26. Tamiz, A. P.; Cai, S. X.; Zhou, Z. L.; Yuen, P. W.; Schelkun, R. M.; Whittemore, E. R.; Weber, E.; Woodward, R. M.; Keana, J. F. W. Structure-activity relationship of N-(phenylalkyl)cinnamides as novel NR2B subtype-selective NMDA receptor antagonists. J. Med. Chem. 1999, 42, 3412-3420.
27. Kitaori, K.; Furukawa, Y.; Yoshimoto, H.; Otera, J. CsF in organic synthesis. Regioselective nucleophilic reactions of phenols with oxiranes leading to enantiopure beta-blockers. Tetrahedron 1999, 55, 14381-14390.
28. Sajiki, H.; Hattori, K.; Hirota, K. The formation of a novel Pd/C-ethylenediamine complex catalyst: chemoselective hydrogenation without deprotection of the O-benzyl and N-Cbz groups. J. Org. Chem. 1998, 63, 7990-7992.
29. Sajiki, H.; Hattori, K.; Hirota, K. Highly chemoselective hydrogenation with retention of the epoxide function using a heterogeneous Pd/C: efhylenediamine catalyst and THF. Chem.-Eur. J. 2000, 6, 2200-2204.
30. Choi, W. B.; Wilson, L. J.; Yeola, S.; Liotta, D. C.; Schinazi, R. F. In Situ Complexation Directs the Stereochemistry of N-Glycosylation in the Synthesis of Oxathiolanyl and Dioxolanyl Nucleoside Analogs. J. Am. Chem. Soc. 1991, 113, 9377-9379.
31. Connors, S. P.; Gill, E. W.; Terrar, D. A. Actions and Mechanisms of Action of Novel Analogs of Sotalol on Guinea Pig and Rabbit Ventricular Cells. Br. J. Pharmacol. 1992, 106, 958-965.
32. Ilyin, V. I.; Whittemore, E. R.; Guastella, J.; Weber, E.; Woodward, R. M. Subtype-selective inhibition of N-methyl-D-aspartate receptors by haloperidol. Mol. Pharmacol. 1996, 50, 1541-1550.
33. Kew, J. N.; Trube, G.; Kemp, J. A. A novel mechanism of activity-dependent NMDA receptor antagonism describes the effect of ifenprodil in rat cultured cortical neurones. J. Physiol. (London) 1996, 497, 761-772.
34. Kew, J. N. C.; Trube, G.; Kemp, J. A. State-dependent NMDA receptor antagonism by Ro 8-4304, a novel NR2B selective, non-competitive, voltage-independent antagonist. Br. J. Pharmacol. 1998, 123, 463-472.
35. Masuko, T.; Kashiwagi, K.; Kuno, T.; Nguyen, N. D.; Pahk, A. J.; Fukuchi, J.; Igarashi, K.; Williams, K. A regulatory domain (R1-R2) in the amino terminus of the N-methyl-D-aspartate receptor: Effects of spermine, protons, and ifenprodil, and structural similarity to bacterial leucine/isoleucine/valine binding protein. Mol. Pharmacol. 1999, 55, 957-969.
36. Gallagher, M. J.; Huang, H.; Lynch, D. R. Modulation of the N-methyl-D-aspartate receptor by haloperidol: NR2B-specific interactions. J. Neurochem. 1998, 70, 2120-2128.
37. Wong, E.; Ng, F. M.; Yu, C. Y.; Lim, P.; Lim, L. H.; Traynelis, S. F.; Low, C. M. Expression and characterization of soluble amino-terminal domain of NR2B subunit of N-methyl-D-aspartate receptor. Protein Sci. 2005, 14, 2275-2283.
38. Rachline, J.; Perin-Dureau, F.; Le Goff, A.; Neyton, J.; Paoletti, P. The micromolar zinc-binding domain on the NMDA receptor subunit NR2B. J. Neurosci. 2005, 25, 308-317.
39. Pfeiffer, C. C. Optical Isomerism and Pharmacological Action, a Generalization. Science 1956, 124, 29-31.
40. Mesecar, A. D.; Koshland, D. E. A new model for protein stereospecificity. Nature 2000, 408, 668.
41. Mezzetti, A.; Schrag, J. D.; Cheong, C. S.; Kazlauskas, R. J. Mirror-image packing in enantiomer discrimination: Molecular basis for the enantioselectivity of B-cepacia lipase toward 2-methyl-3-phenyl-1-propanol. Chem. Biol. 2005, 12, 427-437.
42. Omega, version 2.0; Openeye Scientific Software, Inc.: Santa Fe, NM, 2006.
43. Hawkins, P. C. D.; Skillman, A. G.; Nicholls, A. Comparison of Shape-Matching and Docking as virtual Screening Tools. J. Med. Chem. 2007, 50, 74-82.
44. EON, version 1.1; OpenEye Scientific Software, Inc.: Santa Fe, NM, 2006.
45. Nicholls, A.; MacCuish, N. E.; MacCuish, J. D. Variable Selection and Model Validation of 2D and 3D Molecular Descriptors. J. Comput.-Aided. Mol. Des. 2004, 18, 451-474.
46. Nicholls, A.; Grant, J. A. Molecular shape and electrostatics in the encoding of relevant chemical information. J. Comput.-Aided. Mol. Des. 2005, 19, 661-686.
47. Geballe, M.; Traynelis, S. F.; Snyder, J. P. unpublished.
48. McCauley, J. A.; Theberge, C. R.; Romano, J. J.; Billings, S. B.; Anderson, K. D.; Claremon, D. A.; Freidinger, R. M.; Bednar, R. A.; Mosser, S. D.; Gaul, S. L.; Connolly, T. M.; Condra, C. L.; Xia, M. H.; Cunningham, M. E.; Bednar, B.; Stump, G. L.; Lynch, J. J.; Macaulay, A.; Wafford, K. A.; Koblan, K. S.; Liverton, N. J. NR2B-selective N-Methyl-D-aspartate antagonists: synthesis and evaluation of 5-substituted benzimidazoles. J. Med. Chem. 2004, 47, 2089-2096.
49. Whetsell, W. O. Current concepts of excitotoxicity. J. Neuropath. Exp. Neur. 1996, 55, 1-13.
50. Dirnagl, U.; Iadecola, C.; Moskowitz, M. A. Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci. 1999, 22, 391-397.
51. Brauner-Osborne, H.; Egebjerg, J.; Nielsen, E. O.; Madsen, U.; Krogsgaard-Larsen, P. Ligands for glutamate receptors: design and therapeutic prospects. J. Med. Chem. 2000, 43, 2609-2645.
52. Choi, D. W.; Mauluccigedde, M.; Kriegstein, A. R. Glutamate Neurotoxicity in Cortical Cell Culture. J. Neurosci. 1987, 7, 357-368.
53. Koh, J. Y.; Choi, D. W. Quantitative Determination of Glutamate Mediated Cortical Neuronal Injury in Cell Culture by Lactate-Dehydrogenase Efflux Assay. J. Neurosci. Methods 1987, 20, 83-90.
54. Park, C. K.; Nehls, D. G.; Graham, D. I.; Teasdale, G. M.; Mcculloch, J. The Glutamate Antagonist MK-801 Reduces Focal Ischemic Brain Damage in the Rat. Ann. Neurol. 1988, 24, 543-551.
55. Miyabe, M.; Kirsch, J. R.; Nishikawa, T.; Koehler, R. C.; Traystman, R. J. Comparative analysis of brain protection by N-methyl-D- aspartate receptor antagonists after transient focal ischemia in cats. Crit. Care Med. 1997, 25, 1037-1043.
56. Dogan, A.; Rao, A. M.; Baskaya, M. K.; Rao, V. L. R.; Rastl, J.; Donaldson, D.; Dempsey, R. J. Effects of ifenprodil, a polyamine site NMDA receptor antagonist on reperfusion injury after transient focal cerebral ischemia. J. Neurosurg. 1997, 87, 921-926.
57. Bradford, H. Glutamate, GABA, and epilepsy. Prog. Neurobiol 1995, 47, 477-511.
58. Kohl, B. K.; Dannhardt, G. The NMDA receptor complex: a promising target for novel antiepileptic strategies. Curr. Med. Chem. 2001, 8, 1275-1289.
59. Wlaz, P.; Ebert, U.; Loscher, W. Anticonvulsant effects of eliprodil alone or combined with the glycine(B) receptor antagonist L-701324 or the competitive NMDA antagonist CGP 40116 in the amygdala kindling model in rats. Neuropharmacology 1999, 38, 243-251.
60. Gill, R.; Alanine, A.; Bourson, A.; Buttelmann, B.; Fischer, G.; Heitz, M. P.; Kew, J. N. C.; Levet-Trafit, B.; Lorez, H. P.; Malherbe, P.; Miss, M. T.; Mutel, V.; Pinard, E.; Roever, S.; Schmitt, M.; Trube, G.; Wybrecht, R.; Wyler, R.; Kemp, J. A. Pharmacological characterization of Ro 63-1908 (1-[2-(4-hydroxy-phenoxy)-ethyl]-4-(4-methyl-benzyl)-piperidin-4-ol), a novel subtype-selective N-methyl-D-aspartate antagonist. J. Pharmacol. Exp. Ther. 2002, 302, 940-948.
61. McNamara, J. O. Drugs Effective in the Therapies of the Epilepsies, 10th ed.; McGraw Hill: New York, 2001; pp 521-547.
62. Ellison, G. The N-Methyl-D-Aspartate Antagonists Phencyclidine, Ketamine and Dizocilpine as Both Behavioral and Anatomical Models of the Dementias. Brain Res. Rev. 1995, 20, 250-267.
63. Thornberg, S. A.; Saklad, S. R. Review of NMDA receptors and the phencyclidine model of schizophrenia. Pharmacotherapy 1996, 16, 82-93.
64. Andine, P.; Widermark, N.; Axelsson, R.; Nyberg, G.; Olofsson, U.; Martensson, E.; Sandberg, M. Characterization of MK-801-induced behavior as a putative rat model of psychosis. J. Pharmacol. Exp. Ther. 1999, 290, 1393-1408.
65. Tricklebank, M. D.; Singh, L.; Oles, R. J.; Preston, C.; Iversen, S. D. The Behavioral Effects of MK-801: A Comparison with Antagonists Acting Noncompetitively and Competitively at the NMDA Receptor. Eur. J. Pharmacol. 1989, 167, 127-135.
66. Hiramatsu, M.; Cho, A. K.; Nabeshima, T. Comparison of the Behavioral and Biochemical Effects of the NMDA Receptor Antagonists, MK-801 and Phencyclidine. Eur. J. Pharmacol. 1989, 166, 359-366.
67. Boyce, S.; Wyatt, A.; Webb, J. K.; O'Donnell, R.; Mason, G.; Rigby, M.; Sirinathsinghji, D.; Hill, R. G.; Rupniak, N. M. J. Selective NMDA NR2B antagonists induce antinociception without motor dysfunction: correlation with restricted localisation of NR2B subunit in dorsal horn. Neuropharmacology 1999, 38, 611-623.
68. Loschmann, P. A.; De Groote, C.; Smith, L.; Wullner, U.; Fischer, G.; Kemp, J. A.; Jenner, P.; Klockgether, T. Antiparkinsonian activity of Ro 25-6981, a NR2B subunit specific NMDA receptor antagonist, in animal models of Parkinson's disease. Exp. Neurol. 2004, 187, 86-93.
69. Halgren, T. A. Merck molecular force field 0.1. Basis, form, scope, parameterization, and performance of MMFF94. J. Comput. Chem. 1996, 17, 490-519.
70. Halgren, T. A. Merck molecular force field 0.2. MMFF94 van der Waals and electrostatic parameters for intermolecular interactions. J. Comput. Chem. 1996, 17, 520-552.
71. Halgren, T. A. Merck molecular force field 0.3. Molecular geometries and vibrational frequencies for MMFF94. J. Comput. Chem. 1996, 17, 553-586.
72. Halgren, T. A. Merck molecular force field 0.5. Extension of MMFF94 using experimental data, additional computational data, and empirical rules. J. Comput. Chem. 1996, 17, 616-641.
73. Halgren, T. A.; Nachbar, R. B. Merck molecular force field 0.4. Conformational energies and geometries for MMFF94. J. Comput. Chem. 1996, 17, 587-615.
74. Traynelis, S. F.; Burgess, M. F.; Zheng, F.; Lyuboslavsky, P.; Powers, J. L. Control of voltage-independent zinc inhibition of NMDA receptors by the NR1 subunit. J. Neurosci. 1998, 18, 6163-6175.
75. Junge, C. E.; Sugawara, T.; Mannaioni, G.; Alagarsamy, S.; Conn, P. J.; Brat, D. J.; Chan, P. H.; Traynelis, S. F. The contribution of protease-activated receptor 1 to neuronal damage caused by transient focal cerebral ischemia. Proc. Natl. Acad. Sci. U.S.A. 2003, 100, 13019-13024.
76. Kalinichev, M.; White, D. A.; Hotlzman, S. G. Individual differences in locomotor reactivity to a novel environment and sensitivity to opioid drugs in the rat. I. Expression of morphine-induced locomotor sensitization. Psychopharmacology 2004, 1777, 61-67.
77. Jorgensen, W. L. The Many Roles of Computation in Drug Discovery. Science 2004, 303, 1813-1818.
78. Finlayson, K.; Turnbull, L.; January, C. T.; Sharkey, J.; Kelly, J. S. [3H]Dofetilide binding to HERG transfected membranes: a potential high throughput preclinical screen. Eur. J. Pharmacol. 2001, 430, 147-148.
79. Greengrass, P.; Bremner, R. Binding characteristics of 3H-prazosin to rat brain a-adrenergic receptors. Eur. J. Pharmacol. 1979, 55, 323-326.