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The European College of Neuropsychopharmacology (ECNP) Medicines Chest Initiative: Rationale and Promise

Abstract

Development of drugs for treating diseases of the central nervous system (CNS) has had some of the highest attrition rates in the pharmaceutical industry, and the high risk and cost of development has led to many companies withdrawing from the area, despite significant unmet medical needs remaining and, hence, large commercial potential. For many CNS diseases, particularly psychiatric diseases, our understanding of the fundamental neuroscience associated with the disease is limited, which has led to a lack of predictivity of animal models and, therefore, often a failure of translation from animal models into human patients. Fortunately, technologies such as genetics and functional imaging are rapidly advancing our understanding of the human brain. Historically, many drugs used to treat CNS disorders were discovered by serendipity, when activity was noticed in the clinic during use for another indication. Such clinical ‘repurposing’ of drugs is still a highly useful strategy, but requires the availability of selective and potent tool compounds, with an accompanying regulatory data package, that will allow their use in people. Many such compounds exist within pharmaceutical companies but are sitting on the shelf because their development has been terminated. The Medicines Chest initiative was set up, funded by the European College of Neuropsychopharmacology (ECNP), in order to gain access to such compounds, so they could be used by academics and small companies in experimental medicine studies. The purpose of this article is to provide an update on progress with this initiative.

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References

  1. Angelman Syndrome Foundation. Upcoming Angelman syndrome clinical trial. http://www.angelman.org/news/upcoming-angelman-syndrome-clinical-trial/. Accessed 13 Aug 2015.

  2. Brown R, Basheer R, McKenna J, Strecker R, McCarley R. Control of sleep and wakefulness. Physiol Rev. 2012;92:1087–187.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Cheng YD, Al-Khoury L, Zivin JA. Neuroprotection for ischemic stroke: two decades of success and failure. NeuroRx. 2004;1:36–45.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Davie CA. A review of Parkinson’s disease. Br Med Bull. 2008;86:109–27.

    Article  CAS  PubMed  Google Scholar 

  5. Eder D. CEE-03-310 CeNeS pharmaceuticals. Curr Opin Investig Drugs. 2002;3:284–8.

    CAS  PubMed  Google Scholar 

  6. Enna SJ, Williams M. Challenges in the search for drugs to treat central nervous system disorders. J Pharmacol Exp Ther. 2009;329:404–11.

    Article  CAS  PubMed  Google Scholar 

  7. Escudero I, Johnstone M. Genetics of schizophrenia. Curr Psychiatry Rep. 2014;16:502.

    Article  PubMed  Google Scholar 

  8. ECNP. ECNP Medicines Chest. http://www.ecnp.eu/projects-initiatives/ECNP-medicines-chest.aspx. Accessed 13 Aug 2015.

  9. Fletcher A, Forster E, Bill D, Brown G, Cliffe I, Hartley J, et al. Electrophysiological, biochemical, neurohormonal and behavioural studies with WAY-100635, a potent, selective and silent 5-HT1A receptor antagonist. Behav Brain Res. 1996;73:337–53.

    Article  CAS  PubMed  Google Scholar 

  10. Giardina W, Williams M. Adrogolide HCl (ABT-431; DAS-431), a prodrug of the dopamine D1 receptor agonist, A-86929: preclinical pharmacology and clinical data. CNS Drug Rev. 2001;7:305–16.

    Article  CAS  PubMed  Google Scholar 

  11. Gruber O, Chadha Santuccione A, Aach H. Magnetic resonance imaging in studying schizophrenia, negative symptoms, and the glutamate system. Front Psychiatry. 2014;5:32.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Halliday C, Jones B, Skingle M, Walsh D, Wise H, Tyers M. The pharmacology of fluparoxan: a selective alpha 2-adrenoceptor antagonist. Br J Pharmacol. 1991;102:887–95.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Lankford D, Corser B, Zheng Y, Li Z, Snavely D, Lines C, et al. Effect of gaboxadol on sleep in adult and elderly patients with primary insomnia: results from two randomized, placebo-controlled, 30-night polysomnography studies. Sleep. 2008;31:1359–70.

    PubMed Central  PubMed  Google Scholar 

  14. Le Bon O, Lion K, Verbanck P, Kornreich C. Fluparoxan in male erectile disorder: a case report. J Psychopharmacol. 1995;9:67–8.

    Article  PubMed  Google Scholar 

  15. McCulloch J. Excitatory amino acid antagonists and their potential for the treatment of ischaemic brain damage in man. Br J Clin Pharmacol. 1992;34:106–14.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Meera P, Wallner M, Otis TS. Molecular basis for the high THIP/gaboxadol sensitivity of extrasynaptic GABA(A) receptors. J Neurophysiol. 2011;106:2057–64.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Nutt D, Wilson S, Lingford-Hughes A, Myers J, Papadopoulos A, Muthukumaraswamy S. Differences between magnetoencephalographic (MEG) spectral profiles of drugs acting on GABA at synaptic and extrasynaptic sites: a study in healthy volunteers. Neuropharmacology. 2015;88:155–63.

    Article  CAS  PubMed  Google Scholar 

  18. Olpe H, Karlsson G, Pozza M, Brugger F, Steinmann M, Van Riezen H, et al. CGP 35348: a centrally active blocker of GABAB receptors. Eur J Pharmacol. 1990;187:27–38.

    Article  CAS  PubMed  Google Scholar 

  19. Raasch W. Central nervous system drug market. In: Wikinvest. http://www.wikinvest.com/wiki/Central_Nervous_System_Drug_Market. Accessed 13 Aug 2015.

  20. Seletti B, Benkelfat C, Blier P, Annable L, Gilbert F, de Montigny C. Serotonin1A receptor activation by flesinoxan in humans. Body temperature and neuroendocrine responses. Neuropsychopharmacology. 1995;13:93–104.

    Article  CAS  PubMed  Google Scholar 

  21. Wafford K, Ebert B. Gaboxadol—a new awakening in sleep. Curr Opin Pharmacol. 2006;6:30–6.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to acknowledge the contribution of Dr. Gavin Kilpatrick in helping to set up the Medicines Chest.

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Correspondence to Ann Hayes.

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No funding was received for the publication of this article.

Conflict of interest

David Nutt has no conflicts of interest to report. Ann Hayes has received consulting fees and expenses from the European College of Neuropsychopharmacology (ECNP) for setting up the Medicines Chest.

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Hayes, A., Nutt, D. The European College of Neuropsychopharmacology (ECNP) Medicines Chest Initiative: Rationale and Promise. Pharm Med 29, 269–273 (2015). https://doi.org/10.1007/s40290-015-0111-9

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  • DOI: https://doi.org/10.1007/s40290-015-0111-9

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