From basic to clinical neuropharmacology: Targetophilia or pharmacodynamics?

British Journal of Clinical Pharmacology

Volumn 73, Issue 6, 2012, Pages 959-967

  Green, A Richard ^a   Aronson, Jeffrey K ^b  

^a UNIVERSITY OF NOTTINGHAM   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

4 PHOSPHONOMETHYLPIPECOLIC ACID; ALPHA ADRENERGIC RECEPTOR; AMPA RECEPTOR; APTIGANEL; BIOLOGICAL MARKER; CHLORDIAZEPOXIDE; CHOLINERGIC RECEPTOR; CLOMETHIAZOLE; CLOZAPINE; CYCLOSPORIN A; DIAZEPAM; DOPAMINE RECEPTOR; ENLIMOMAB; HISTAMINE RECEPTOR; LUBELUZOLE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; NEUROTRANSMITTER; NORADRENALIN; NORCLOZAPINE; OPIATE RECEPTOR; PHENOTHIAZINE DERIVATIVE; PSYCHOTROPIC AGENT; QUETIAPINE; RESERPINE; RILUZOLE; SEROTONIN; SEROTONIN UPTAKE INHIBITOR; TRICYCLIC ANTIDEPRESSANT AGENT; TRIPLE REUPTAKE INHIBITOR; UNINDEXED DRUG;

BRAIN INFARCTION; CLINICAL PHARMACOLOGY; CLINICAL TRIAL (TOPIC); DEPRESSION; DOUBLE BLIND PROCEDURE; DRUG SCREENING; EXCITOTOXICITY; HUMAN; INFLAMMATION; MOOD DISORDER; NEUROPHARMACOLOGY; NEUROPROTECTION; NONHUMAN; NOTE; PHARMACODYNAMICS; PHARMACOEPIDEMIOLOGY; PHARMACOGENETICS; PRIORITY JOURNAL; SCHIZOPHRENIA; STROKE;

CLINICAL TRIALS AS TOPIC; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; HUMANS; MODELS, ANIMAL; NEUROPHARMACOLOGY; PHARMACEUTICAL PREPARATIONS;

EID: 84860691680     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/j.1365-2125.2012.04246.x     Document Type: Note

References (51)

1. Bush V. Science - the Endless Frontier. A Report to the President on a Program for Postwar Scientific Research. Washington, DC: Office of Scientific Research and Development, 1945.
2. Stokes DE. Pasteur's Quadrant. Basic Science and Technological Innovation. Washington, DC: Brookings Institution Press, 1997.
3. Ostrowski J, Wyrwicz LS. Integrating genomics, proteomics and bioinformatics in translational studies of molecular medicine. Expert Rev Mol Diagn 2009; 9: 623-30.
4. Noble D. The Music of Life. Biology Beyond the Genome. Oxford: Oxford University Press, 2006.
5. Aronson JK. A manifesto for clinical pharmacology from principles to practice. Br J Clin Pharmacol 2010; 70: 3-13.
6. Green AR. Neuropharmacology of 5-hydroxytryptamine. Br J Pharmacol 2006; 147: S145-52.
7. Delay J, Deniker P, Hart JM. Utilisation en therapeutique psychiatrique d'une phénothiazine d'action centrale élective. Ann Med Psychol (Paris) 1952; 110: 112-7.
8. Weber E. Schockbekampfung mit Megaphen am Unfallort. [Control of shock with megaphen at the place of the accident. Langenbecks Arch Klin Chir Ver Dtsch Z Chir 1954; 279: 791-3.
9. Green AR. Gaddum and LSD: the birth and growth of experimental and clinical neuropharmacology research on 5-HT in the UK. Br J Pharmacol 2008; 154: 1583-99.
10. Gaddum JH. Discoveries in therapeutics. J Pharm Pharmacol 1954; 6: 497-512.
11. Enna SJ, Williams M. Challenges in the search for drugs to treat central nervous system disorders. J Pharmacol Exp Ther 2009; 329: 404-11.
12. van Gerven J, Cohen A. Vanishing clinical psychopharmacology. Br J Clin Pharmacol 2011; 72: 1-5.
13. Enna SJ, Bennett JP Jr, Burt DR, Creese I, Snyder SH. Stereospecificity of interaction of neuroleptic drugs with neurotransmitters and correlation with clinical potency. Nature 1976; 263: 338-41.
14. Willner P. The validity of animal models of depression. Psychopharmacology 1984; 83: 1-16.
15. Geyer MA, Markou A. The role of preclinical models in the development of psychotropic drugs. In: Psychopharmacology: the Fifth Generation of Progress, eds Davis KL, Coyle JT, Nemeroff C. Philadelphia: Lipincott, Williams and Wilkins, 2002; 445-55.
16. Geyer MA, Markou A. Animal models of psychiatric disorders. In: Psychopharmacology: the Fourth Generation of Progress, eds Bloom FE, Kupfer DJ. New York: Raven Press, 1995; 787-98.
17. Spedding M, Jay T, Costa e Silva J, Perret L. A pathophysiological paradigm for the therapy of psychiatric disease. Nat Rev Drug Discov 2005; 4: 467-74.
18. Markou A, Chiamulera C, Geyer MA, Tricklebank M, Steckler T. Removing obstacles in neuroscience drug discovery: the future path for animal models. Neuropsychopharmacol Rev 2009; 34: 74-89.
19. Horrobin DF. Modern biomedical research: an internally self-consistent universe with little contact with medical reality? Nat Rev Drug Discov 2003; 2: 151-4.
20. Macrae IM. Principles of translational neuropharmacology: animal models of stroke. Br J Pharmacol 2011; 164: 1062-78.
21. Constantinescu CS, Farooqi N, O'Brien K, Gran B. Experimental autoimmune encephalomyelitis as a model for multiple sclerosis (MS). Br J Pharmacol 2011; 164: 1079-106.
22. Wickens JR, Hyland BI, Tripp G. Animal models to guide clinical drug development in ADHD: lost in translation? Br J Pharmacol 2011; 164: 1107-28.
23. Nuechterlein KH, Green MF, Kern RS, Baade LE, Barch DM, Cohen JD, Essock S, Fenton WS, Frese FJ III, Gold JM, Goldberg T, Heaton RK, Keefe RS, Kraemer H, Mesholam-Gately R, Seidman LJ, Stover E, Weinberger DR, Young AS, Zalcman S, Marder SR. The MATRICS Consensus Cognitive Battery, part 1: test selection, reliability, and validity. Am J Psychiatry 2008; 165: 203-13.
24. Kern RS, Nuechterlein KH, Green MF, Baade LE, Fenton WS, Gold JM, Keefe RS, Mesholam-Gately R, Mintz J, Seidman LJ, Stover E, Marder SR. The MATRICS Consensus Cognitive Battery, part 2: co-norming and standardization. Am J Psychiatry 2008; 165: 214-20.
25. Porsolt RD, Anton G, Blavet N, Jalfre M. 'Behavioural despair' in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol 1978; 47: 379-91.
26. Cryan JF, Sweeney FF. The age of anxiety: role of animal models of anxiolytic action in drug discovery. Br J Pharmacol 2011; 164: 1129-61.
27. Jones CA, Watson DJG, Fone KCF. Animal models of schizophrenia. Br J Pharmacol 2011; 164: 1162-94.
28. Grahame-Smith DG. 'Keep on taking the tablets': pharmacological adaptation during long-term drug therapy. Br J Clin Pharmacol 1997; 44: 227-38.
29. Gajwani P, Muzina DJ, Kemp DE, Gao K, Calabrese JR. Update on quetiapine in the treatment of bipolar disorder: results from the BOLDER studies. Neuropsychiatr Dis Treat 2007; 3: 847-53.
30. Fineberg NA, Chamberlain SR, Hollander E, Boulougouris V, Robbins TW. Translational approaches to obsessive-compulsive disorder: from animal models to clinical treatment. Br J Pharmacol 2011; 164: 1044-61.
31. Green AR, Ashwood T, Odergren T, Jackson DM. Nitrones as neuroprotective agents in cerebral ischemia with particular reference to NXY-059. Pharmacol Ther 2003; 100: 195-214.
32. Green AR. Pharmacological approaches to acute ischaemic stroke: reperfusion certainly, neuroprotection possibly. Br J Pharmacol 2008; 153: S325-38.
33. O'Collins VE, Macleod MR, Donnan GA, Horky LL, van der Worp BH, Howells DW. 1026 experimental treatments in acute stroke. Ann Neurol 2006; 59: 467-77.
34. Stroke Therapy Academic Industry Roundtable (STAIR). Recommendations for standards regarding preclinical neuroprotective and restorative drug development. Stroke 1999; 30: 2752-8.
35. Green AR, Shuaib A. Therapeutic strategies for the treatment of stroke. Drug Discov Today 2006; 11: 681-93.
36. Lees KR, Zivin JA, Ashwood T, Davalos A, Davis SM, Diener H-C, Grotta J, Lyden P, Shuaib A, Hårdemark HG, Wasiewski WW, Stroke-Acute Ischemic NXY Treatment (SAINT I) Trial Investigators. NXY-059 for acute ischemic stroke. N Engl J Med 2006; 354: 588-99.
37. Shuaib A, Lees KR, Lyden P, Grotta J, Davalos A, Davis SMD, Diener HC, Ashwood T, Wasiewski WW, Emeribe U, SAINT II Trial Investigators. NXY-059 for the treatment of acute ischemic stroke. N Engl J Med 2007; 357: 562-71.
38. Diener HC, Lees KR, Lyden P, Grotta J, Davalos A, Davis SM, Shuaib A, Ashwood T, Wasiewski W, Alderfer V, Hårdemark HG, Rodichok L. NXY-059 for the treatment of acute stroke: pooled analysis of the SAINT I and II Trials. Stroke 2008; 39: 1751-8.
39. Lo EH. Experimental models, neurovascular mechanisms and translational issues in stroke research. Br J Pharmacol 2008; 153: S396-405.
40. Donnan G, Davis SM. Stroke drug development. Usually but not always, animal models. Stroke 2005; 36: 2326.
41. Fisher M, Tatlisumak T. Use of animal models has not contributed to development of acute stroke therapies: con. Stroke 2005; 36: 2324-5.
42. Kaste M. Use of animal models has not contributed to development of acute stroke therapies: pro. Stroke 2005; 36: 2323-4.
43. Green AR, Odergren T, Ashwood T. Animal models of stroke: do they have value for discovering neuroprotective agents? Trends Pharmacol Sci 2003; 24: 402-8.
44. Bath PMW, Gray LJ, Bath AJG, Buchan AM, Miyata T, Green AR. Effects of NXY-059 in experimental stroke: an individual animal meta-analysis. Br J Pharmacol 2009; 157: 1157-71.
45. Davis M, Mendelow AD, Perry RH, Chambers IR, James OF. Experimental stroke and neuroprotection in the aging rat brain. Stroke 1995; 26: 1072-8.
46. Schaller BJ. Influence of age on stroke and preconditioning-induced ischemic tolerance in the brain. Exp Neurol 2007; 205: 9-19.
47. Bath PMW, Macleod MR, Green AR. Emulating multicentre clinical stroke trials: a new paradigm for studying novel interventions in experimental models of stroke. Int J Stroke 2009; 4: 471-9.
48. Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies. 'CAMARADES'. Available at (last accessed 17 March 2012).
49. Gabrielsson J, Green AR. Quantitative pharmacology or pharmacokinetic pharmacodynamic integration should be a vital component in integrative pharmacology. J Pharmacol Exp Ther 2009; 331: 767-74.
50. Green AR, Gabrielsson J, Fone KCF. Translational neuropharmacology and the appropriate and effective use of animal models. Br J Pharmacol 2011; 164: 1041-3.
51. Sjoerdsma AG. Starting with Serotonin. Silver Spring, MD: Improbable Books, 2008; 617.