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Chapter 7 - Medicinal chemistry challenges in the design of next generation antidepressants

Published online by Cambridge University Press:  19 October 2021

By
David P. Rotella
Edited by
Chad E. Beyer  and
Stephen M. Stahl
Chad E. Beyer
Affiliation:
University of Colorado School of Medicine
Stephen M. Stahl
Affiliation:
University of California, San Diego
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Summary

Monoamine-based strategies and targets have provided a useful variety of therapeutic agents with beneficial activity in the treatment of depression. However, this approach has some limitations, including a delayed onset of efficacy and treatment resistance. As a result, there is significant interest in non-monoamine targets and their potential as antidepressants. This search for new treatment modalities has been aided by better understanding of the neurochemical pathways involved in mood. This chapter will review medicinal chemistry advances in a selection of non-monoamine targets of current interest in the field.

Type
Chapter
Information
Next Generation Antidepressants
Moving Beyond Monoamines to Discover Novel Treatment Strategies for Mood Disorders
 , pp. 102 - 118
Publisher: Cambridge University Press
Print publication year: 2010

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References

Kelly, J., Curr. Med. Chem. Cent. Nerv. Syst. Agents, 2003, 3, 311.CrossRefGoogle Scholar
Butler, S. G., Meegan, M. J. Curr. Med. Chem., 2008, 15, 1737.Google Scholar
Abramets, I. I., Evdokimov, D. V., Talalaenko, A. N., Neurophysiology, 2007, 39, 184.CrossRefGoogle Scholar
Demyttenaere, K., De Fruyt, J., Stahl, S. M., Int. J. Neuropsychopharmacol., 2005, 8, 93.CrossRefGoogle Scholar
Katz, M. M., Tekell, J. L., Bowden, C. L., Brannan, S., Houston, J. P., Berman, N., Neuropsychopharmacology, 2004, 29, 566.CrossRefGoogle Scholar
Posternak, M. A., Zimmerman, M., J. Clin. Psychiatry, 2005, 66, 148.CrossRefGoogle Scholar
Blier, P., Montigny, C., Biol. Psychiatry, 1998, 44, 213.CrossRefGoogle Scholar
Manji, H. K., Chen, G., Mol. Psychiatry, 2002, 7, S46.CrossRefGoogle Scholar
Wong, M. L., Licinio, J., Nat. Rev. Drug Discov., 2004, 3, 136.CrossRefGoogle Scholar
Xu, H., Richardson, J. S., Li, X. M., Neuropsychopharmacology, 2003, 28, 53.Google Scholar
Gonul, A. S., Doksat, K., Eker, C., Eker, O. D., Trends Serotonin Uptake Inhibitor Res, 2005, 1.Google Scholar
Manji, H. K., Drevets, W. C., Chamey, D. S., Nat. Med., 2001, 7, 541.Google Scholar
Coyle, J. T., Duman, R. S., Neuron, 2003, 38, 157.CrossRefGoogle Scholar
Rosenzweig-Lipson, S., Beyer, C. E., Hughes, Z., et al., Pharmacol. Ther., 2007, 113, 134.Google Scholar
Cipriani, A., Barbui, C., Brambilla, P., Furukawa, T. A., Hotopf, M., Geddes, J. R., J. Clin. Psychiatry, 2006, 67, 850.Google Scholar
Thase, M. E., J. Clin. Psychiatry, 1998, 59, 502.CrossRefGoogle Scholar
DeMontigny, C., Chaput, I., Blier, P., J. Clin. Psychopharmacol., 1987, 7, 24.Google Scholar
Romero, L., Hervás, I., Artegas, F., Neurosci. Lett., 1996, 219, 123.Google Scholar
Duxon, M. S., Starr, K. R., Upton, N., Br. J. Pharmacol., 2000, 130, 1713.CrossRefGoogle Scholar
Takeuchi, K., Kohn, T. J., Honigschmidt, N. A., et al., Bioorg. Med. Chem. Lett., 2003, 13, 1903.CrossRefGoogle Scholar
Takeuchi, K., Kohn, T. J., Honigschmidt, N. A., et al., Bioorg. Med. Chem. Lett., 2006, 16, 2347.Google Scholar
Hatzenbuhler, N. T., Evrard, D. A., Harrison, B. L., et al., J. Med. Chem., 2006, 49, 4785.CrossRefGoogle Scholar
Hatzenbuhler, N. T., Baudy, R., Evrard, D. A., et al., J. Med. Chem., 2008, 51, 6980.CrossRefGoogle Scholar
Kreiss, D. S., Lucki, I., J. Pharmacol. Exp. Ther., 1995, 274, 866.Google Scholar
Atkinson, P. J., Bromidge, S. M., Duxon, M. S., et al., Bioorg. Med. Chem. Lett., 2005, 15, 737.CrossRefGoogle Scholar
Scott, C., Soffin, E. M., Hill, M., et al., Eur. J. Pharmacol., 2006, 536, 54.CrossRefGoogle Scholar
Starr, K. R., Price, G. W., Watson, J. M., et al., Neuropsychopharmacology, 2007, 32, 2163.CrossRefGoogle Scholar
Skolnick, P., Popik, P, Janowsky, A., Beer, B., Lippa, A. S., Eur. J. Pharmacol., 2003, 461, 99.CrossRefGoogle Scholar
D’Aquila, P. S., Collu, M., Gessa, G. L., Serra, G., Eur. J. Pharmacol., 2000, 405, 365.Google Scholar
Naranjo, C., Tremblay, L. K., Busto, U. E., Prog. Neuropsychopharmacol. Biol. Psychiatry, 2001, 25, 781.Google Scholar
Skolnick, P., Popik, P., Janowsky, A., Beer, B., Lippa, A. S., Life Sci., 2003, 73, 3175.Google Scholar
Ben-Jonathan, N., Hnasko, R., Endocr. Rev., 2001, 22, 724.Google Scholar
Breuer, M. E., Chan, J. S. W., Oosting, R. S., et al., Eur. Neuropsychopharmacol., 2008, 18, 908.Google Scholar
Carlier, P. R., Lo, M. M., Lo, P. C., et al., Bioorg. Med. Chem. Lett., 1998, 8, 487.Google Scholar
Liang, Y., Shaw, A. M., Boules, M., et al., J. Pharmacol. Exp. Ther., 2008, 327, 573.CrossRefGoogle Scholar
Aluisio, L., Lord, B., Barbier, A., et al., Eur. J. Pharmacol., 2008, 587, 141.Google Scholar
Bannwart, L. M., Carter, D. S., Cai, H. Y., et al., Bioorg. Med. Chem. Lett., 2008, 18, 6062.CrossRefGoogle Scholar
Trullas, R., Skolnick, P., Eur. J. Pharmacol., 1990, 185, 1.Google Scholar
Paul, I. A., Layer, R. T., Skolnick, P, Nowak, G., Eur. J. Pharmacol., 1993, 247, 305.CrossRefGoogle Scholar
Paul, I. A., Nowak, G., Layer, R. T., Skolnick, P., J. Pharmacol. Exp. Ther., 1994, 269, 95.Google Scholar
Nowak, G., Legutko, B., Skolnick, P., Popik, P., Eur. J. Pharmacol., 1998, 342, 367.Google Scholar
Zarate, C. A., Singh, J. B., Carlson, P. J., et al., Arch. Gen. Psychiatry, 2006, 63, 856.Google Scholar
Pilc, A., Chaki, S., Nowak, G., Witkin, J. M., Biochem. Pharmacol., 2008, 75, 997.Google Scholar
Lea, P. M., Faden, A. I., CNS Drug Rev., 2006, 12, 149.CrossRefGoogle Scholar
Li, X., Need, A. B., Baez, M., Witkin, J. M., J. Pharmacol. Exp. Ther., 2006, 319, 254.Google Scholar
Sharma, S., Rodriguez, A. L., Conn, J. P., Lindsley, C. W., Bioorg. Med. Chem. Lett., 2008, 18, 4098.Google Scholar
Porter, R. H. P., Jaeschke, G., Spooren, W., et al., J. Pharmacol. Exp. Ther., 2005, 315, 711.Google Scholar
Rodriguez, A. L., Nong, Y., Sekaran, N. K., Alagille, D., Tamagnan, G. D., Conn, P. J., Mol. Pharmacol., 2005, 68, 793.Google Scholar
Milbank, J. B. J., Knauer, C. S., Augelli-Szafran, C. E., et al., Bioorg. Med. Chem. Lett., 2007, 17, 4415.CrossRefGoogle Scholar
Bach, P., Nilsson, K., Svensson, T., et al., Bioorg. Med. Chem. Lett., 2006, 16, 4788.Google Scholar
Ohishi, H., Shigemoto, R., Nakanishi, S., Mizuno, N., Neuroscience, 1993, 53, 1009.CrossRefGoogle Scholar
Tanabe, Y., Nomura, A., Masu, M., Shigemoto, R., Mizuno, N., J. Neurosci., 1993, 13, 1372.Google Scholar
Shigemoto, R., Kinoshita, A., Wada, E., et al., J. Neurosci., 1997, 17, 7503.CrossRefGoogle Scholar
Ohishi, H., Shigemoto, R., Nakanishi, S., Mizuno, N., J. Comp. Neurol., 1993, 335, 252.Google Scholar
Spinelli, S., Ballard, T., Gatti-McArthur, S., et al., Psychopharmacology, 2005, 179, 292.Google Scholar
Higgins, G. A., Ballard, T. M., Kew, J. N. C., et al., Neuropharmacology, 2004, 46, 907.Google Scholar
Woltering, T. J., Adam, G., Alanine, A., et al., Bioorg. Med. Chem. Lett., 2007, 17, 6811.Google Scholar
Woltering, T. J., Adam, G., Wichmann, J., et al., Bioorg. Med. Chem. Lett., 2008, 18, 1091.Google Scholar
Nakazato, A., Sakagami, K., Yasuhara, A., et al., J. Med. Chem., 2004, 47, 4570.CrossRefGoogle Scholar
Yasuhara, A., Nakamura, M., Sakagami, K., et al., Bioorg. Med. Chem., 2006, 14, 4193.CrossRefGoogle Scholar
Reinschied, R., CNS Neurol Disord Drug Targets, 2006, 5, 219.Google Scholar
Jenck, F., Wichmann, J., Dautzenberg, F. M., et al., Proc. Natl Acad. Sci., 2000, 97, 4938.CrossRefGoogle Scholar
Varty, G. B., Lu, S. X., Morgan, C. A., et al., J. Pharmacol. Exp. Ther., 2008, 326, 672.Google Scholar
Spagnolo, B., Carrà, G., Fantin, M., et al., J. Pharmacol. Exp. Ther., 2007, 321, 961.CrossRefGoogle Scholar
Rizzi, A., Gavioli, E. C., Marzola, G., et al., J. Pharmacol. Exp. Ther., 2007, 321, 968.Google Scholar
Schatzberg, A. F., Rothschild, A. J., Langlais, P. J., Bird, E. D., Cole, J. O., J. Psychiatr. Res., 1985, 19, 57.CrossRefGoogle Scholar
Marshall, R. D., Blanco, C., Printz, D., Liebowitz, M. R., Klein, D. F., Coplan, J., Psychiatry Res., 2002, 110, 219.Google Scholar
Zobel, A. W., Nickel, T., Sonntag, A., Uhr, M., Holsboer, F., Ising, M., J. Psychiatr. Res., 2001, 35, 83.CrossRefGoogle Scholar
Thomson, F., Craighead, M., Neurochem. Res., 2008, 33, 691.Google Scholar
Erickson, K., Drevets, W., Schulkin, J., Neurosci. Biobehav. Rev., 2003, 27, 233.CrossRefGoogle Scholar
Ray, N. C., Clark, R. D., Clark, D. E., et al., Bioorg. Med. Chem. Lett., 2007, 17, 4901.Google Scholar
Clark, R. D., Ray, N. C., Williams, K., et al., Bioorg. Med. Chem. Lett., 2008, 18, 1312.Google Scholar
Shah, N., Scanlan, T., Bioorg. Med. Chem. Lett., 2004, 14, 5199.Google Scholar
Spiga, F., Harrison, L. R., Wood, S. A., et al., J. Neuroendocrinology, 2007, 19, 891.CrossRefGoogle Scholar
Bachmann, C. G., Bilang-Bleuel, A., De Carli, S, Linthorst, A. C. E., Reul, J. M. H. M., Neuroendocrinology, 2005, 81, 129.CrossRefGoogle Scholar
de Winter, R. F., van Hemert, A. M., DeRijk, R. H., et al., Neuropsychopharmacology, 2003, 28, 140.Google Scholar
van Londen, L., Goekoop, J. G., van Kempen, G. M., et al., Neuropsychopharmacology, 1993, 17, 284Google Scholar
Purba, J. S., Hoogendijk, W. J., Hofman, M. A., Swaab, D. F., Arch. Gen. Psychiatry, 1996, 53, 137.Google Scholar
Serradeil-Le Gal, C., Wagnon, J., Simiand, J., et al., J. Pharmacol. Exp. Ther., 2002, 300, 1122.Google Scholar
Griffante, C., Green, A., Curcuruto, O., Haslam, C. P., Dickinson, B. A., Arban, R., Br. J. Pharmacol., 2005, 146, 744.Google Scholar
Iijima, M., Chaki, S., Prog. Neuropsychopharmacol. Biol. Psych., 2007, 31, 622.Google Scholar
Louis, C., Cohen, C., Depoortére, R., Griebel, R., Neuropsychopharmacology, 2006, 31, 2180.CrossRefGoogle Scholar
Mountjoy, K. G., Mortrud, M. T., Low, M. J., Simerly, R. B., Cone, R. D., Mol. Endocrinol. 1994, 8, 1298.Google Scholar
Chhajlani, V., Biochem. Mol. Biol. Int., 1996, 38, 73.Google Scholar
Adan, R. A., Szklarczyk, A. W., Oosterom, J., et al., Eur. J. Pharmacol., 1999, 378, 249.CrossRefGoogle Scholar
Yamano, Y., Yoshioka, M., Toda, Y., et al., J. Vet. Med. Sci., 2004, 66, 1323.Google Scholar
Chaki, S., Hirota, S., Funakoshi, T., et al., J. Pharmacol. Exp. Ther., 2003, 304, 818.CrossRefGoogle Scholar
Nozawa, D., Okubo, T., Ishii, T., et al., Bioorg. Med. Chem., 2007, 15, 1989.CrossRefGoogle Scholar

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