Display options
Cite
Gilles C, Schunck T, Erb G, et al. Human models as tools in the development of psychotropic drugs. Dialogues Clin Neurosci. 2002;4(4):377-87
Gilles, C., Schunck, T., Erb, G., Namer, I. J., Hodé, Y., Nedelec, J. F., Boeijinga, P., Luthringer, R., & Mâcher, J. P. (2002). Human models as tools in the development of psychotropic drugs. Dialogues in clinical neuroscience, 4(4), 377-87.
Gilles, Christian, et al. "Human models as tools in the development of psychotropic drugs." Dialogues in clinical neuroscience vol. 4,4 (2002): 377-87.
Gilles C, Schunck T, Erb G, Namer IJ, Hodé Y, Nedelec JF, Boeijinga P, Luthringer R, Mâcher JP. Human models as tools in the development of psychotropic drugs. Dialogues Clin Neurosci. 2002 Dec;4(4):377-87. PMID: 22034241; PMCID: PMC3181700.
Copy Download .nbib Format: NLM
Share it on

Dialogues Clin Neurosci. 2002 Dec;4(4):377-87.

Human models as tools in the development of psychotropic drugs.

Dialogues in clinical neuroscience

Christian Gilles, Thérèse Schunck, Gilles Erb, Izzie Jacques Namer, Yann Hodé, Jean-François Nedelec, Peter Boeijinga, Remy Luthringer, Jean-Paul Mâcher

Affiliations

  1. FORENAP, Institute for Research in Neuroscience and Neuropsychiatry, Rouffach, France.

PMID: 22034241 PMCID: PMC3181700

Abstract

Despite the growing means devoted to research and development (R α D) and refinements in the preclinical stages, the efficiency of central nervous system (CMS) drug development is disappointing. Many drugs reach patient studies with an erroneous therapeutic indication andlor in incorrect doses. Apart from the first clinical studies, which are conducted in healthy volunteers and focus only on safety, iolerability, and pharmacokinetics, drug development mostly relies on patient studies. Psychiatric disorders are characterized by heterogeneity and a high rate of comorbidity. It is becoming increasingly difficult to recruit patients for clinical trials and there are many confounding factors in this population, for example, those related to treatments. In order to keep patient exposure and financial expenditure to a minimum, it is important to avoid ill-designed and inconclusive studies. This risk could be minimized by gathering pharmacodynamic data earlier in development and considering that the goal of a phase 1 plan is to reach patient studies with clear ideas about the compound's pharmacodynamic profile, its efficacy in the putative indication (proof of concept), and pharmacokinetic/pharmacodynamic relationships, in addition to safety, tolerability, and pharmacokinetics. Human models in healthy volunteers may be useful tools for this purpose, but their use necessitates a global adaptation of the phase scheme, favoring pharmacodynamic assessments without neglecting safety. We are engaged in an R α D program aimed to adapt existing models and develop new paradigms suitable for early proof of concept substantiation.

Keywords: Alzheimer's disease; anxiety; depression; drug development; healthy volunteer; model; proof of concept; schizophrenia

References

  1. Psychopharmacology (Berl). 1994 Mar;114(2):257-61 - PubMed
  2. Psychopharmacology (Berl). 1996 May;125(1):50-6 - PubMed
  3. Psychopharmacology (Berl). 1992;107(2-3):437-41 - PubMed
  4. Neurobiol Aging. 1992 Mar-Apr;13(2):313-8 - PubMed
  5. Life Sci. 1985 Jul 15;37(2):193-7 - PubMed
  6. Arch Gen Psychiatry. 1991 Jul;48(7):603-10 - PubMed
  7. Neuropsychopharmacology. 2001 Nov;25(5):699-703 - PubMed
  8. Neuropsychopharmacology. 2002 Aug;27(2):282-92 - PubMed
  9. Br J Clin Pharmacol. 1999 Sep;48(3):323-30 - PubMed
  10. Biol Psychiatry. 2000 Oct 1;48(7):627-40 - PubMed
  11. J Clin Psychopharmacol. 1985 Apr;5(2):70-7 - PubMed
  12. Nature. 1984 Nov 22-28;312(5992):363-4 - PubMed
  13. Depress Anxiety. 1998;8(1):1-7 - PubMed
  14. Arch Gen Psychiatry. 1989 Jun;46(6):511-7 - PubMed
  15. Trends Cogn Sci. 2002 Sep 1;6(9):394 - PubMed
  16. Eur J Clin Invest. 1998 Nov;28(11):944-9 - PubMed
  17. Dialogues Clin Neurosci. 2002 Dec;4(4):432-7 - PubMed
  18. Am J Psychiatry. 1998 Feb;155(2):280-2 - PubMed
  19. Dialogues Clin Neurosci. 2000 Sep;2(3):247-55 - PubMed
  20. Neuron. 1998 May;20(5):937-45 - PubMed
  21. Am J Psychiatry. 1995 Aug;152(8):1180-4 - PubMed
  22. Clin Pharmacokinet. 1992 Sep;23(3):191-215 - PubMed
  23. Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):455-60 - PubMed
  24. Biol Psychiatry. 1997 Aug 1;42(3):206-12 - PubMed
  25. J Neural Transm (Vienna). 1996;103(7):873-81 - PubMed
  26. Neuropsychopharmacology. 1999 Feb;20(2):177-87 - PubMed
  27. Dialogues Clin Neurosci. 2002 Dec;4(4):342-50 - PubMed
  28. Psychiatry Res. 1998 May 20;82(2):115-27 - PubMed
  29. J Neural Transm Suppl. 1989;28:91-102 - PubMed
  30. J Psychopharmacol. 1999 Dec;13(4):385-90 - PubMed
  31. Psychopharmacology (Berl). 1996 Feb;123(4):361-73 - PubMed
  32. Neuropsychopharmacology. 1998 Jan;18(1):18-25 - PubMed
  33. Psychopharmacology (Berl). 1988;95(2):208-15 - PubMed
  34. Biol Psychiatry. 1999 Apr 1;45(7):872-82 - PubMed
  35. Psychopharmacology (Berl). 1985;87(2):247-9 - PubMed
  36. Ann N Y Acad Sci. 1991;640:268-71 - PubMed
  37. Ann N Y Acad Sci. 1991;640:241-4 - PubMed
  38. J Neurosci. 2001 Sep 1;21(17):6846-52 - PubMed
  39. Mov Disord. 1995 Jan;10(1):28-36 - PubMed
  40. Neuropsychopharmacology. 2000 Oct;23(4):428-38 - PubMed
  41. Biol Psychiatry. 1998 Sep 1;44(5):364-6 - PubMed
  42. Br J Clin Pharmacol. 1990 Dec;30(6):795-803 - PubMed
  43. Psychopharmacology (Berl). 1998 Feb;135(3):213-29 - PubMed
  44. Psychopharmacology (Berl). 1999 Jul;145(2):193-204 - PubMed
  45. J Psychiatr Res. 2000 Jan-Feb;34(1):35-43 - PubMed
  46. Biol Psychiatry. 1998 Jun 1;43(11):811-6 - PubMed
  47. Isr J Psychiatry Relat Sci. 1991;28(3):32-41 - PubMed
  48. Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6512-6 - PubMed
  49. Acta Psychiatr Scand Suppl. 1990;360:71-2 - PubMed
  50. J Psychopharmacol. 1990 Jan;4(4):219-32 - PubMed
  51. Br J Clin Pharmacol. 1997 Sep;44(3):219-25 - PubMed
  52. Neuropsychopharmacology. 1995 Aug;13(1):9-19 - PubMed
  53. Eur Neuropsychopharmacol. 1999 Jan;9(1-2):149-55 - PubMed
  54. Brain Res Bull. 2000 Feb;51(3):213-8 - PubMed
  55. Ann N Y Acad Sci. 1985;444:359-69 - PubMed
  56. J Psychiatry Neurosci. 1991 Jul;16(2):91-5 - PubMed
  57. Neuropsychobiology. 1999;39(1):49-56 - PubMed
  58. Neuron. 1998 May;20(5):947-57 - PubMed
  59. Psychopharmacology (Berl). 1998 Jan;135(1):27-36 - PubMed
  60. Arch Gen Psychiatry. 1987 May;44(5):418-26 - PubMed
  61. Psychiatry Res. 1996 Jul 31;67(2):113-22 - PubMed
  62. Anesth Analg. 1975 Mar-Apr;54(2):169-72 - PubMed
  63. Prog Brain Res. 1998;116:421-37 - PubMed
  64. Psychopharmacology (Berl). 1995 Jun;119(3):315-24 - PubMed
  65. Biol Psychiatry. 1995 Dec 1;38(11):742-6 - PubMed
  66. Eur Neuropsychopharmacol. 2000 Sep;10(5):419-21 - PubMed
  67. Psychopharmacology (Berl). 1993;110(4):421-6 - PubMed
  68. Neuroreport. 1995 Sep 11;6(13):1723-8 - PubMed
  69. Neuron. 1999 Jun;23(2):229-32 - PubMed
  70. Biol Psychiatry. 1997 Oct 15;42(8):664-8 - PubMed
  71. J Geriatr Psychiatry Neurol. 1992 Apr-Jun;5(2):72-7 - PubMed
  72. Med Biol. 1979;57(6):402-5 - PubMed
  73. Behav Biol. 1977 Sep;21(1):1-31 - PubMed
  74. Psychopharmacology (Berl). 1977 Mar 23;52(1):1-6 - PubMed
  75. J Clin Psychopharmacol. 1983 Oct;3(5):310-3 - PubMed
  76. Science. 2000 Dec 22;290(5500):2315-9 - PubMed
  77. Psychopharmacology (Berl). 1990;100(1):84-9 - PubMed
  78. Brain Res Brain Res Rev. 1992 Sep-Dec;17(3):215-26 - PubMed
  79. Psychopharmacology (Berl). 1991;103(1):83-90 - PubMed
  80. Psychopharmacology (Berl). 1987;92(3):358-64 - PubMed
  81. Psychopharmacology (Berl). 1991;105(1):1-8 - PubMed
  82. Psychopharmacol Bull. 1996;32(4):637-46 - PubMed
  83. Neuropsychopharmacology. 2001 Oct;25(4):455-67 - PubMed
  84. Pharmacol Biochem Behav. 1979 Feb;10(2):205-10 - PubMed
  85. Neurosci Biobehav Rev. 1985 Spring;9(1):87-94 - PubMed
  86. Synapse. 1998 Jun;29(2):142-7 - PubMed
  87. J Clin Psychopharmacol. 1995 Feb;15(1):58-62 - PubMed
  88. J Psychiatr Res. 2002 Jan-Feb;36(1):1-6 - PubMed
  89. Int J Clin Pharmacol Ther Toxicol. 1991 Mar;29(3):103-7 - PubMed
  90. Eur Neuropsychopharmacol. 1991 May;1(2):137-41 - PubMed
  91. Arch Gen Psychiatry. 1994 Mar;51(3):199-214 - PubMed
  92. Psychopharmacology (Berl). 1989;98(4):487-94 - PubMed
  93. Am J Psychiatry. 1998 Feb;155(2):283-5 - PubMed
  94. Neuropsychobiology. 1996;34(2):98-105 - PubMed
  95. Neuropsychobiology. 1999 Nov;40(4):207-13 - PubMed
  96. Neuropsychopharmacology. 1999 Feb;20(2):106-18 - PubMed
  97. Biol Psychiatry. 1998 Dec 15;44(12):1229-38 - PubMed
  98. J Pharmacol Exp Ther. 1992 Mar;260(3):1209-13 - PubMed
  99. Arch Gen Psychiatry. 2001 Apr;58(4):371-7 - PubMed
  100. Neuropsychopharmacology. 1996 May;14(5):301-7 - PubMed
  101. Anaesthesia. 1980 Jul 7;35(7):669-75 - PubMed
  102. Eur J Clin Pharmacol. 1991;41(3):225-31 - PubMed
  103. Am J Psychiatry. 1993 Dec;150(12):1881-3 - PubMed
  104. Biol Psychiatry. 1999 Oct 15;46(8):1060-80 - PubMed
  105. Prog Neuropsychopharmacol Biol Psychiatry. 1985;9(5-6):651-4 - PubMed

Publication Types