Jean-Charles Schwartz Explained

Jean-Charles Schwartz, born on May 28, 1936, in Paris, is a French neurobiologist, pharmacist and researcher. Husband of Ketty Schwartz, née Gersen (1937–2007) and father of Olivier, Marc and Emmanuelle. He is a member of the Academy of Sciences. He developed pitolisant, the first clinically approved antagonist for H3 receptors.^[1]

Biography

Jean-Charles Schwartz holds a doctorate in pharmacy (Paris, 1960), a doctorate in science (Paris, 1965) and a diploma from the Institut de Pharmacodynamie et Pharmacotechnie (Paris, 1961). He was Professor of Physiology at the Faculties of Pharmacy of the Universities of Haute Normandie and Paris 5-René Descartes (1968–2001) and Professor of Neuropharmacology at the Institut Universitaire de France (1990–2000).

He was a pharmacy internist (1958–1963), assistant at the Central Hospital Pharmacy (1964–1968) and then Chief Pharmacist at the Assistance Public-Hôpitaux de Paris (1968–1999).

He headed the "Neurobiology and Pharmacology" and then "Neurobiology and Molecular Pharmacology" units of the Institut national de la santé et de la recherche médicale (Inserm) from 1972 to 2001.^[2] He was vice-chairman of the Board of Directors of Inserm (1999–2002).

He co-founded with Dr. Jeanne-Marie Lecomte the pharmaceutical research/development and commercialisation companies Bioprojet (1981), Bioprojet Pharma (1992) and Bioprojet Biotech (2001). He is the Scientific Director of Bioprojet since 2001.^[3]

Scientific career

Jean-Charles Schwartz, a specialist in the neurobiology and pharmacology of brain chemical mediators, has discovered and developed new classes of drugs, mainly in neuropsychiatry.

He studied the brain functions of histamine and dopamine. He established the role of histamine as a neurotransmitter in brain:^[4] he described its metabolic pathways, identified the main histaminergic neuronal pathways,^[5] identified and located the receptors (H1, H2 and H3) mediating its actions.^{[6] [7]} His description of the role of histaminergic neurons in vigilance control has contributed to the development of second-generation antihistamines devoid of sedative effects. He discovered the H3 receptor, demonstrated the role of its strong constitutive activity in controlling the activity of cerebral histaminergic neurons,^[8] developed the first selective ligands of this receptor^[9] and developed pitolisant, (Wakix®), a wake-promoting and anticataplectic agent now currently used for the treatment of patients with narcolepsy.^[10]

Having hypothesized the existence of several types of dopamine receptors,^[11] Jean-Charles Schwartz and his collaborators identified by cloning the two splicing isoforms of the D2^[12] receptor, then the D3^[13] receptor. He developed the first selective ligands of the D3 receptor and used them to demonstrate the involvement of this receptor in drug dependence and the action of antipsychotic drugs.^[14] It has shown the involvement of receptor modulations in changes in the effects of chronically administered psychotropic agents, processes responsible for tolerance and dependence.^{[15] [16] [17] [18] [19]}

In the field of neuropeptides, Jean-Charles Schwartz created the concept of "inactivation neuropeptidases" by identifying the enzymes responsible for the metabolic inactivation of enkephalins^[20] and cholecystokininin^[21] and developed the first selective inhibitors of these enzymes, the latters used as research tools and then, from one of them thas therapeutic agent. He has clinically developed racecadotril (Tiorfan®), a neprilysin ("enkephalinase") inhibitor,^[22] the first selective intestinal anti-secretory agent that has been used as an antidiarrheal agent by several million patients.^[23]

He also discovered by cloning several subtypes of brain serotonin receptors (5HT6, 5HT7),^{[24] [25]} and established the neurotransmitter role of anandamide, an endogenous ligand of cannabinoid receptors.^[26]

He is the author of more than 700 publications.^{[27] [28]}

Awards and honours

• Gold medal of internists at the Paris Hospital Boarding School (1962).
• Grand Prize for Chemical and Natural Sciences (1983) and Charles-Léopold-Mayer Grand Prize of the Academy of Sciences - Institut de France (1991)
• Eli-Lilly Prize from the European College of Neuropsychopharmacology (1994).
• Honorary doctorate from the University of Berlin (1997).
• Prize of the Collegium Internationale Neuropsychopharmacologicum (1998).
• Ariëns Prize of the Dutch Society of Pharmacology (1998).
• Galien Prize (2001).
• Laureate of the Institute for Scientific Information "Highly cited researcher" (2001).
• Prize of the Order of Pharmacists of the National Academy of Pharmacy (2002).
• Grand Prize of the Foundation for Medical Research (2009).
• Grand Prize of the National Academy of Pharmacy (2017).
• Knight of the Legion of Honour (2009).

Membership of learned societies

• European College of Neuropsychopharmcology (ECNP)
• International College of Neuropsychopharmacology (CINP)
• American Association for the Advancement of Sciences
• Society of Pharmacology and experimental Therapeutics

Membership of Academies

• Academy of Sciences (2002)^[29]
• Academia Europaea(1994)^[30]

Notes and References

1. http://www.academie-sciences.fr/academie/membre/SchwartzJC_bio0210.pdf l'Académie des sciences CV
2. Web site: Histoire de l'Inserm.
3. Web site: Bioprojet.
4. Web site: Bioprojet.
5. Garbarg M., Barbin G., Feger J. and Schwartz J-C., « An histaminergic pathway in rat brain evidenced by lesions of the medial forebrain bundle », Science, 1974, 186, p. 833-835
6. Baudry M., Martres M.P. and Schwartz J-C., « H1- and H2-receptors in the histamine-induced accumulation of cyclic AMP in guinea-pig cortical slices », Nature, 1975, 253, p. 362-363
7. Arrang J.M., Garbarg M. and Schwartz J-C., « Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor », Nature, 1983, 302, p. 832-837
8. Stark H., Morisset S., Rouleau A., Ligneau X., Gbahou F., Tardivel-Lacombe J., Schunack W., Gavellin G.R., Schwartz J-C. and Arrang J.M., « High constitutive activity of native H3 receptors regulates histamine neurons in brain », Nature, 2000, 408, p. 860-864
9. Arrang J.M., Garbarg M., Lancelot J-C., Lecomte J.M., Pollard H., Robba M., Schunack W. and Schwartz J-C., « Highly potent and selective ligands for histamine H3-receptors », Nature, 1987, 327, p. 117-123
10. Dauvilliers Y, Bassetti C, Lammers GJ, Arnulf I, Mayer G, Rodenbeck A, Lehert P, Ding CL, Lecomte J-M and Schwartz J-C., « Pitolisant versus placebo or modafinil in patients with narcolepsy: a double-blind, randomised trial », Lancet Neurol, 2013; 12, p. 1068–75
11. Sokoloff P., Martres M.P. and Schwartz J-C., « Dopamine autoreceptors and postsynaptic receptors both labelled by 3H-apomorphine », Nature, 1980, 288, p. 283-286
12. Giros B., Sokoloff P., Martres M.P., Riou J.F., Emorine L.J. and Schwartz J-C., « Alternative splicing directs the expression of two D-2 dopamine receptor isoforms », Nature, 1989, 342, p. 923-926
13. Sokoloff P., Giros B., Martres M.P., Bouthenet M.L. and Schwartz J-C., « Molecular cloning and characterisation of a novel dopamine receptor (D3) as a target for neuroleptics », Nature, 1990, 347, p. 146-151
14. Pilla M., Perachon S., Sautel F. Garrido F., Mann A., Wermuth CG, Schwartz J-C, Everitt B.J., Sokoloff P., «Selective inhibition of cocaine-seeking behaviour by a partial dopamine receptor agonist », Nature, 1999; 400: (6742), p. 371-375
15. Schwartz J-C., Martres M.P., Rose C., Quach T.T. and Sokoloff P., Adaptations of neurotransmitter receptor mechanisms in the CNS, in “Chemical Neurotransmission : 75 years” Second Nobel Conference., L. Stjörne, P. Hedgrist, H. Lagercrantz and A. Wennmalm: (Eds) Academic Press, 1981, p. 411-423
16. Costentin J., Protais P. and Schwartz J-C., « Rapid and dissociated changes in sensitivities of different dopamine receptors in mouse brain », Nature, 1975, 257, p. 405
17. Martres M.P., Baudry M. and Schwartz J-C., « Subsensitivity of noradrenaline-stimulated cyclic AMP accumulation in brain slices of d-amphetamine-treated mice », Nature, 1975, 253, p. 731
18. Llorens C., Martres M.P., Baudry M. and Schwartz J-C., « Hypersensitivity to noradrenaline in cortex after chronic morphine : relevance to tolerance and dependence », Nature, 1978, 274, p. 603-605
19. Guillin O., Diaz J., Caroll P., Griffon N., Schwartz J-C. and Sokoloff P., « BDNF controls dopamine D3 receptor expression and triggers behavioral sensitization », Nature, 2001, 411, p. 86-89
20. Malfroy B., Swertz J.P., Guyon A., Roques B.P. and Schwartz J.C., « High affinity enkephalin degrading peptidase in brain increased after morphine», Nature, 1978, 276, p. 523-526
21. Rose C., Vargas F., Facchinetti P., Bourgeat P., Bambal R.B., Bishop P.B., Chan S.M.T., Moore A.N.J. Ganellin C.R. and Schwartz J-C., « Characterization and inhibition of a cholecystokinin-inactivating serine peptidase», Nature, 1996, 380, p. 403-409
22. Roques B.P., Fournié-Zaluski M.C., Soroca E., Lecomte J.M., Malfroy B., Llorens C. and Schwartz J.C., « The enkephalinase inhibitor thiorphan shows antinociceptive activity in mice », Nature, 1980, 288, p. 286-288
23. Roge J, Baumer P, Berard H, Schwartz JC, Lecomte JM., « The enkephalinase inhibitor, acetorphan, in acute diarrhoea. A double-blind, controlled clinical trial versus loperamide. », Scand J Gastroenterol., 1993, 28, p. 352-4
24. Quach T.T., Rose C., Duchemin A.M. and Schwartz J-C., « Glycogenolysis induced by serotonin in brain : identification of a new class of receptor », Nature, 1982, 298, p. 373-375
25. Ruat M., Traiffort E., Leurs R., Tardivel-Lacombe J., Diaz J. Arrang J.M. and Schwartz J-C., « Molecular cloning, characterization and localization of a high affinity serotonin receptor (5-HT7) activating cAMP formation », Proc. Natl. Acad. Sci. USA, 1993, 90, p. 8547-8551
26. Piomelli D., Pilon C., Giros B., Sokoloff P., Martres M.P. and Schwartz J-C., « Dopamine activation of the arachidonic acid cascade as a basis for D1/D2 receptor synergism », Nature, 1991, 353, p. 164-167
27. Web site: Researchgate.
28. Web site: Google scholar.
29. Web site: Académie des sciences.
30. [:fr:Academia Europaea#Biochimie, biologie moléculaire|Academia europaea]