FORECASTING AN EMERGENT SYSTEMIC TREND IN NEUROPHARMACOLOGY
DOI:
https://doi.org/10.24193/subbchem.2021.3.01Keywords:
brain complexity, systems biology, network pharmacology, magic bullet, magic shotgun, multi-mechanistic drug, valproate, levetiracetam, multi-potent drug, poly-therapy.Abstract
Neuropharmacology (NP), which evolved along with scientific medicine, got treatments for several common disorders of the nervous system. But, most of the NP drugs are just symptomatic, reducing only the manifestations of brain pathologies. Also, for main neuro-psychiatric pathologies (e.g. the neurodegenerative diseases) there is very poor or no medication, and the output of NP drug discovery declined in the last decades. This review paper argues that those drawbacks derive from the reductionist NP leaning towards single–target selective drugs, at odds with the essential complexity of brain functioning and the multifactorial causality of its pathologies. Most active neuro-drugs (e.g. valproate and levetiracetam) are in fact multi-mechanistic since they have been selected by phenotypic screening in vivo, not by single-target binding in vitro. A putative solution of the relative NP stagnation seems to come with the emergent systemic approach of network pharmacology. A plausible flowchart of the main stages of a network NP drug discovery endeavor is finally sketched.
References
A. G. Phillips; P. Hongaard-Andersen; R. A. Moscicki; B. Sahakian; R. Quirion; K. R. R. Krishnan; T. Race; Int. J. Neuropsychopharmacol., 2015, 19, 1–16
D. G. Margineanu; BioSystems, 2016, 141, 1–9
E. Shorter; Curr. Opin. Psychiatry, 2008, 21, 593–597
T. A. Ban; Dialogues Clin. Neurosci., 2006, 8, 335–344
B. H. Yokley; M. Hartman; B. S. Slusher; ACS Chem. Neurosci., 2017, 8, 429–431
W. Singer; EMBO Rep., 2007, 8, S16–S19
Q. Mu; Y. Chen; J. Wang; Genomics Proteomics Bioinformatics, 2019, 17, 344–366
J. L. Ji; M. Spronk; K. Kulkarni; G. Repovš; A. Anticevic; M. W. Cole; Neuroimage, 2019, 185, 35–57
S. B. Laughlin; T. J. Sejnowski; Science, 2003, 301, 1870–1874
D. G. Margineanu; Epilepsy Res., 2012, 98, 104–115
T. Takahashi; Prog. Neuropsychopharmacol. Biol. Psychiatry, 2013, 45, 257–265
H. Kitano; Science, 2002, 295, 1662–1664
U. Sauer; M. Heinemann; N. Zamboni; Science, 2007, 316, 550−551
C. T. Keith; A. A. Borisy; B. R. Stockwel; Nature Rev. Drug Discov., 2005, 4, 71–78
A. L. Hopkins; Nature Chem. Biol., 2008, 4, 682–690
B. L Roth; D. J. Sheffler; W. K., Kroeze; Nature Rev. Drug Discov., 2004, 3, 353–359
M. T. Bianchi; J. Pathmanathan; S. S. Cash; Med. Hypotheses, 2009, 72, 297–305
D. G. Margineanu; Epilepsy Behav., 2014, 38, 131–142
J. Arrowsmith; Nature Rev. Drug Discov., 2011, 10, 1
M. T. Bianchi; Med. Hypotheses, 2010, 74, 297–300
D. G. Margineanu; Systems (network) pharmacology for brain functionality restoration. In Homeostatic Control of Brain Function; D. Boison, S. Masino Eds.; Oxford University Press, New York, USA, 2015; pp. 231–247
C.-T. Chiu; Z. Wang; J. G. Hunsberger; D.-M. Chuang; Pharmacol. Rev., 2013, 65, 105–142
S. Chateauvieux; F. Morceau; M. Dicato; M. Diederich; J. Biomed. Biotech., 2010, article ID 479364, doi:10.1155/2010/479364
J. Sun; H. Xu; Z. Zhao; Chem. Biodiv., 2012, 9, 900–910
D. G. Margineanu; H. Klitgaard; Levetiracetam mechanisms of action. In Antiepileptic Drugs, 5th ed.; R. H. Levy, R. H. Mattson, B. S. Meldrum, E. Perucca Eds.; Lippincott Williams & Wilkins, Philadelphia, USA, 2002; pp. 419–427
I. Niespodziany; H. Klitgaard; D.G. Margineanu; Neurosci. Lett., 2001, 306, 5–8
P. Poulain P.; D. G. Margineanu; Neuropharmacol., 2002, 42, 346–352
I. Carunchio; M. Pieri; M. Ciotti; F. Albo; C. Zona; Epilepsia, 2007, 48, 654–662
M. Ängehagen; D. G. Margineanu; E. Ben-Menachem; L. Ronnback; E. Hansson. H. Klitgaard; NeuroReport, 2003, 14, 471–475
M. Madeja; D. G. Margineanu; A. Gorji; E. Siep; P. Boerrigter; H. Klitgaard; E.-J. Speckmann; Neuropharmacol., 2003, 45, 661–671
B. A. Lynch; N. Lambeng; K. Nocka; P. Kensel-Hammes; S. M. Bajjalieh; A. Matagne; B. Fuks; Proc. Nat. Acad. Sci. USA, 2004, 101, 9861–9866
T. De Smedt; R. Raedt; K. Vonck; P. Boon; CNS Drug Reviews, 2007, 13, 57–78
D. G. Margineanu; Rev. Quest. Sci, 2011, 182, 33–52
B. M. Kenda; A. C. Matagne; P.E. Talaga; P. M. Pasau; E. Differding; B. I. Lallemand; A. M. Frycia; F. G. Moureau ; H. V. Klitgaard; M. R. Gillard; B. Fuks; P. Michel; J. Med. Chem., 2004, 47, 530–549
A. C. Matagne; D. G. Margineanu; B. Kenda; P. Michel; H. Klitgaard; Br. J. Pharmacol., 2008, 154, 1662–1671
B. Winblad; CNS Drug Reviews, 2005, 11, 169–182
M. Gillard; B. Fuks; P. Michel; P. Vertongen; R. Massingham; P. Chatelain; Eur. J. Pharmacol., 2003, 478, 1–9
P. von Rosenstiel; Neurotherapeutics, 2007, 4, 84–8
M. A. Rogawski; Br. J. Pharmacol., 2008,154, 1555–1557
A. Golyala; P. Kwan; Seizure, 2017, 44,147–156
D. G. Margineanu; H. Klitgaard; Expert Opin. Drug Discov., 2009, 4, 23–32
W. Löscher; H. Potschka; S. M. Sisodiya; A. Vezzani; Pharmacol. Rev., 2020, 72, 606–638
D. G. Margineanu; Med. Res. Arch., 2021, 9, in press
E. C. Butcher; E. L. Berg; E. Kunkel; Nature Biotechnol., 2004, 22, 1253–1259
M. Keck; G. Androsova; F. Gualtieri; A. Walker; E.-L. von Rüden; V. Russmann; C. A. Deeg; S. M. Hauck; R. Krause; H. Potschka; Neurobiol. Dis., 2017, 105, 164–178
A. B. Elgoyhen; B. Langguth; S. Vanneste; D. DeRidder; Front. Systems Neurosci., 2012, 6, doi: 10.3389/fnsys.2012.00001
K. Shameer; A. Nayarisseri; F. X. R. Duran; H. González-Díaz; Curr. Neuropharmacol., 2017, 15, 1058–1061
A. Talevi; Expert Opin. Drug Discov., 2016, 11, 1001–1016
D. Romeo-Guitart; J. Forés; M. Herrando-Grabulosa; R. Valls; T. Leiva-Rodríguez; E. Galea; F. González-Pérez; X. Navarro; V. Petegnief; A. Bosch; M. Coma; J. M. Mas; C. Casas; Sci. Rep. 2018, 8,1879 doi:10.1038/s41598-018-19767-3
H. Geerts; J. Wikswo; P. H. van der Graaf; J. P.F. Bai; C. Gaiteri; D. Bennett; S. E. Swalley; E. Schuck; R. Kaddurah-Daouk; K. Tsaioun; M. Pelleymounter; CPT Pharmacometrics Syst. Pharmacol., 2020, 9, 5–20.
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