Salomon Z. Langer

Salomon Zender Langer (b. 12 October 1936) is an Argentinian pharmacologist whose family had fled from Poland to Argentina in the early 1930s and were thus saved from the Holocaust during the Second World War.

Dr. Salomon Z. Langer

Career

He was born in Buenos Aires, Argentina and graduated in 1960 from the School of Medicine of Buenos Aires University. Starting in 1963 with a Rockefeller Foundation Fellowship he joined the Department of Pharmacology at Harvard University until the end of 1966. His research was on the mechanisms involving denervation supersensitivity.[1] with Ullrich Trendelenburg[2][3] with whom he became lifelong friends.

He spent two years (1967-1969) in Cambridge, England with de:Leslie Iversen[4][5] and at the Institute of Animal Physiology with Marthe Vogt where he worked on norepinephrine(NE) uptake and the regulation of NE release elicited by nerve stimulation as well as the metabolic fate of the released neurotransmitter.[6] In 1969, Dr. Langer returned to Argentina where he was appointed Director of the Institute for Pharmacological Research.

The work started in Cambridge continued at the Institute in Buenos Aires during the years 1969-1976, leading to the discovery of the presynaptic inhibitory Alpha-adrenoceptors on noradrenergic nerve terminals and their role in the modulation of the NE release during nerve stimulation[7]

In 1974, Dr. Langer discovered the Alpha-2 adrenoceptors[8] and characterized the pharmacological differences between alpha 1-adrenoceptors and alpha 2-adrenoceptors, establishing that the latter corresponded to the presynaptic auto-receptors[9]

During the years 1975-1976, he provided the first extensive and rigorous evidence "in vitro"[10][11] and "in vivo" of co-transmission (NE and ATP) in the cat's nicitating membrane. In the summer of 1976, Dr. Langer became Head of the Department of Pharmacology at the Wellcome Research Laboratories in Beckenham, Kent, UK and in 1976 he was appointed Director of Biology at fr:Sanofi-Synthélabo Research in Paris where he was later became the Research Director and Vice-President.

The research team directed by Dr. Langer discovered between the years 1979-1980 a specific, high-affinity binding site labeled with for 3H-imipramine[12] and later with 3H-paroxetine,[13] which is associated with the serotonin transporter in the brain and in blood platelets of various species, including man. 3H-paroxetine binding was subsequently used as a marker in the purification of the serotonin transporter for cloning and expression.

Throughout the 80's Dr. Langer continued his work on presynaptic autoreceptors regulating NE, DA and 5-HT release and reported the interactions in neurotransmission between the neuronal transporter and the corresponding autoreceptor.

During the 23 years at Synthelabo, Dr. Langer discovered and developed five compounds : diltiazem, a calcium antagonist (for coronary insufficiency); betaxolol, a beta-1 adrenoceptor selective antagonist for hypertension and also for local use in the treatment of glaucoma; zolpidem , a selective full agonist of the alpha-1 subunit of the benzodiazepine-GABA-A receptor (for insomnia) and mizolastine, a peripherally acting histamine H-1 receptor antagonist which also inhibits the formation of leukotriens(for allergic diseases).

In 2000, Dr. Langer moved to Israel where he continued research projects in drug discovery for major depression and Alzheimer's disease. In 2014, Dr. Langer founded the drug company Synaptic Pharma Ltd to develop Eliprodil, a noncompetitive antagonist of the ionotropic NMDA receptor for a rapid onset antidepressant action in severely drug-resistant depressed patients.

Discoveries

Langer was the first to describe pre-synaptic autoreceptors for DA, 5HT, ACh, GABA and glutamate.[14][15] He was among the first to demonstrate co-transmission in the 1970s [16] and also played a pivotal role in developing the atypical antipsychotic, aripiprazole.[17]

Awards and prizes

Throughout his career Dr. Langer received many awards and prizes.

  • 1962: Rockefeller Foundation Fellowship
  • 1976: Guggenheim Fellowship for research in cardiovascular pharmacology
  • 1977: Gaddum Memorial Lecture Award[18] by the British Pharmacological Society
  • 1980: G.E. Brown Memorial Lecture[19] of the American Heart Association
  • 1981:First International Prize of the Anna-Monika Foundation[20] (Dortmund, West Germany) for research in the field of endogenous depression.
  • 1986: Pythagoras Prize in Pharmacology. Mediterranea University of Reggio Calabria, Calabria, Italy.
  • 1991:Otto Krayer Award in Pharmacology, presented by ASPET (American Society of Pharmacology and Experimental Therapeutics)
  • 1991: Ciba Award[21] in Hypertension, presented by the Council for High Blood Pressure of the American Heart Association, USA.
  • 1993: Eli Lilly Award in Neuroscience[22] from the European College of Neuropsychopharmacology(ECNP).
  • 1999: Lieber Prize in Schizophrenia[23] presented by the National Alliance for Research on Schizophrenia and Depression (NARSAD), USA.
  • 2000: ASPET Award[24] of the American Society for Pharmacology and Experimental Therapeutics.
  • 2002: Julius Axelrod Award Medal[25] for research in the field of Catecholamines (ASPET).
  • 2009: Mark Nickerson Memorial Lecture[26] at McGill University, Montreal, Quebec, Canada.
  • 2009:Inaugural Norman Weiner Memorial Award[27] by the International College of Neurophychopharmacology (CINP)
  • 2010: Pioneers in Psychopharmacology Award[28] by the in International College of Neurophsychopharmacology (CINP)

Publications

Dr. Langer is among the highly cited researchers in Pharmacology during the period of 1981-1999:ISI Highly cited. He is editor of several books and member of the editorial boards of several scientific journals. Dr. Langer has published more than 450 scientific articles and is holder of at least 21 patents in France, the United States and Japan.

Positions

In 1974, Dr. Langer was president of the Latin American Society of Pharmacology (ALF). From 1989 to 1992 he was president of the European College of Neuropsychopharmacology (ECNP) and from 1991 to 1998 he served as Vice-President of the International College of Neurophsychopharmacology (CINP) and was member of the Executive Committee of the World Federation of Societies of Biological Psychiatry (WFSPB) from 1991 to 1997. For the period of 2002 to 2006, Dr. Langer was the Treasurer and member of the Executive Committee of IUPHAR and between 2006 and 2010 First Vice President of IUPHAR.

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References
  1. The onset of denervation supersensitivity. Langer SZ, Trendelenburg U. J Pharmacol Exp Ther. 1966 Jan;151(1):73-86
  2. Demonstration by the histochemical fluorescence method of the prolonged disappearance of catecholamines from the denervated nictitating membrane of the cat. Weiner N, Langer SZ, Trendelenburg U. J Pharmacol Exp Ther. 1967 Aug;157(2):284-9
  3. Time course of the development of supersensitivity to various amines in the nictitating membrane of the pithed cat after denervation or decentralization. Langer SZ, Draskóczy PR, Trendelenburg U. J Pharmacol Exp Ther. 1967 Aug;157(2):255-73.
  4. Effects of phenoxybenzamine on the uptake and metabolism of noradrenaline in the rat heart and vas deferens. Iversen LL, Langer SZ. Br J Pharmacol. 1969 Nov;37(3):627-37.
  5. Monoamine oxidase and catechol-O-methyl transferase activities in cat nictitating membrane and rat and guinea-pig vas deferens after sympathectomy. Iversen LL, Jarrott B, Langer SZ. Br J Pharmacol. 1968 Nov;34(3):693P-694P.
  6. Noradrenaline release from isolated muscles of the nictitating membrane of the cat S. Z. Langer, Marthe Vogt J. Physiol. 1971 April; 214(1): 159–171.
  7. Possible physiological significance of the initial step in the catabolism of noradrenaline in the central nervous system of the rat M. B. Farah, E. Adler-Graschinsky, S. Z. Langer: Naunyn-schmiedebergs Archives of Pharmacology - NAUNYN-SCHMIED ARCH PHARMACOL vol. 297, no. 2, pp. 119-131, 1977
  8. Evidence for the presynaptic location of the alpha-adrenoceptors which regulate noradrenaline release in the rat submaxillary gland Ester J. Filinger, S. Z. Langer, C. J. Perec, F. J. E. Stefano Naunyn-schmiedebergs Archives of Pharmacology - NAUNYN-SCHMIED ARCH PHARMACOL vol. 304, no. 1, pp. 21-26, 1978
  9. Physiological significance of α-adrenoceptor-mediated negative feedback mechanism regulating noradrenaline release during nerve stimulation S. Z. LANGER, Edda Adler-Graschinsky, O. Giorgi. Nature , vol. 265, no. 5595, pp. 648-650, 1977
  10. The effects of the 2-amino-tetrahydronaphthalene derivative M7, a selective α 2 -adrenoceptor agonist in vitro N. B. Shepperson, S. Z. Langer Naunyn-schmiedebergs Archives of Pharmacology - NAUNYN-SCHMIED ARCH PHARMACOL, vol. 318, no. 1, pp. 10-13, 1981
  11. In vitro studies on 6-fluoronoradrenaline at several peripheral sympathetic neuroeffector junctions N. B. Shepperson, T. Purcell, R. Massingham, S. Z. Langer Naunyn-schmiedebergs Archives of Pharmacology - NAUNYN-SCHMIED ARCH PHARMACOL ,
  12. ASSOCIATION OF HIGH AFFINITY 3H-IMIPRAMINE BINDING SITES WITH THE SEROTONIN TRANSPORTER; POSSIBLE ROLE OF ENDOGENOUS MODULATORS S. Z. Langer, S. Arbilla, L Tahraoui, C. R. Lee Clinical Neuropharmacology - CLIN NEUROPHARMACOL , vol. 7, 1984
  13. Stereoselectivity in the metabolism of 3H-noradrenaline during uptake into and efflux from the isolated rat vas deferens K.-H. Graefe, F. J. E. Stefano, S. Z. Langer: Naunyn-schmiedebergs Archives of Pharmacology - NAUNYN-SCHMIED ARCH PHARMACOL vol. 299, no. 3, pp. 225-238, 1977
  14. Presynaptic regulation of catecholamine release.Langer SZ Biochem Pharmacol 1974;23:1793-800
  15. Presynaptic regulation of monoaminergic neurons. Meltzer Hy, editor Psychopharmacology.The third Generation of Progress.New York: Raven Press; 1987 p.151-8
  16. Possible involvement of a transmitter different from norepinephrine in residual responses to nerve stimulation of cat nictitating membrane after pre-treatment with reserpine. Langer SZ. J.Pharmacol Exp Ther 1976;196:697-713/
  17. Presynaptic regulation of the release of catecholamines. Lager SZ.Pharmacl Reviews 1980; 32:337-62.
  18. "BPS - Gaddum Memorial Award". Bps.ac.uk. Retrieved 20 October 2017.
  19. "BCVS George E. Brown Memorial Lecture". Professional.heart.org. Retrieved 20 October 2017.
  20. "Award Winners - Anna Monika Stiftung - Page 5". Anna-monika-stiftung.de. Retrieved 20 October 2017.
  21. "CBI Award for Hypertension Work" (pDF). Hyper.ahajournals.org. Retrieved 20 October 2017.
  24. "ASPET - Pharmacia-ASPET Award for Experimental Therapeutics". Aspet.org. Retrieved 20 October 2017.
  25. "ASPET - Julius Axelrod Award in Pharmacology". Aspet.org. Retrieved 20 October 2017.
  26. "Archived copy". Archived from the original on 19 August 2016. Retrieved 6 August 2016.CS1 maint: archived copy as title (link)
  27. "ASPET - Past Norman Weiner Lectures". Aspet.org. Retrieved 20 October 2017.
  28. "CINP 2010 Congress Awards – CINP". Cinp.org. Retrieved 20 October 2017.
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