Miodrag Radulovacki Explained

Miodrag Radulovacki
Birth Date:28 April 1933
Birth Place:Parage, Kingdom of Yugoslavia
Death Place:Belgrade, Serbia
Nationality:Serbian
Education:Karlovci High School, Serbia
Alma Mater:Medical Faculty, University of Belgrade, Serbia, (MD), (Ph.D.)
Field:Neuropharmacology, Sleep and sleep disorders, Sleep-related breathing disorders
Work Institutions:University of Belgrade, Serbia
UCLA – Brain Research Institute, 1964-1965
University of Khartoum, Sudan, 1967-1970
College of Medicine at the University of Illinois at Chicago (UIC), 1970 - 2014
Known For:Adenosine Sleep Theory, 1984
Pharmacological Approaches in the Treatment of Sleep Apnea
Yugoslav Student Summer Program at the University of Illinois at Chicago and Champaign-Urbana, 1990-2000
The Miodrag Radulovacki Family Prize for Excellence in Basic Sciences at the UIC College of Medicine, 2005
Prizes:Inventor of the Year Award, 2010, College of Medicine at the University of Illinois at Chicago
Foreign Member of the Serbian Academy of Sciences and Arts, 2003, Belgrade, Serbia

Miodrag (Misha) Radulovacki (Serbian Cyrillic: Миодраг Радуловачки; Serbian Latin: Miodrag Radulovački), was a Serbian American scientist and inventor. He was Professor of Pharmacology in the College of Medicine at the University of Illinois at Chicago (UIC),[1] Radulovacki's research accomplishments include: (1) the Adenosine Sleep Theory,[2] and (2) pioneering pharmacological studies for the treatment of sleep apnea,[3] together with research collaborator, David W. Carley,[4] (Professor of Medicine at the UIC). Radulovacki and Carley invented several drug therapies for the treatment of sleep apnea which have been patented by the UIC. The UIC recognized them as the 2010 "Inventors of the Year."[5] [6] Radulovacki published more than 170 scientific papers.[7] Radulovacki was also a Foreign Member of the Serbian Academy of Sciences and Arts.[8]

Early life

Miodrag Radulovacki was born on April 28, 1933, in Parage, a village in northwestern Serbia. Both of his parents were elementary school teachers. At the beginning of World War II, Radulovacki's father was drafted into the Yugoslav Army and was later taken prisoner by the invading Germans.

In 1943, Radulovacki moved to Sremski Karlovci after his mother accepted a teaching position in the town. Sremski Karlovci (also known as Karlovci), a baroque Serbian town on the banks of the Danube River, had been home to the Radulovacki family for over 200 years. Radulovacki attended Karlovci High School or "Gymnasium," which is the oldest high school in Serbia. Radulovacki called Karlovci Gymnasium the "Serbian Cambridge and Oxford". Radulovacki graduated as valedictorian of the Karlovci High School Class of 1951. Radulovacki gained admission to the University of Belgrade School of Medicine.

Education and scientific career

Radulovacki graduated from the University of Belgrade School of Medicine in 1959.[9] [10] [11] He went on to obtain a PhD in Neurophysiology. The topic of his PhD thesis was: "Sleep in Split-Brain Cats," partly done at the Brain Research Institute at UCLA.

Radulovacki spent 18 months at the University of California, Los Angeles (UCLA) Brain Research Institute[12] where his mentor was Ross Adey.[13] One of the findings of his research at UCLA was that the electroencephalographic (EEG) pattern of sleep in cats with split brain to the pons is synchronous in both brain hemispheres, indicating the importance of the brainstem in sleep regulation.[14]

In 1966, Radulovacki accepted a teaching position with the Physiology Department in the College of Medicine at the University of Khartoum, Sudan. There he invented an approach for obtaining cerebrospinal fluid using a cannula to the cisterna magna in the brain of cats. The cannulation method enabled researchers to obtain cerebrospinal fluid during sleep and wakefulness for the analysis of monoamine metabolites.[15] This approach was of interest since Michel Jouvet's Monoamine Theory of Sleep,[16] with serotonin as the sleep inducing agent, was dominant at the time. From 1970 to 1984, at the University of Illinois, Radulovacki published a series of papers dealing with the role of monoamines in sleep.

In 1970, Radulovacki was recruited by Klaus Unna[17] to join the Department of Pharmacology in the College of Medicine at the University of Illinois at Chicago as an Assistant Professor. Radulovacki published more than 170 scientific papers during his career at the UIC.

Scientific achievements

Adenosine Sleep Theory

In 1984, Radulovacki postulated the Adenosine Sleep Theory, (JPET, 228: 268-274, 1984).[18] The idea for adenosine's role in sleep occurred to him after reading a paper by Sol Snyder's group (Proc. Natl. Acad. Sci, 78: 3260-64, 1981)[19] about the importance of adenosine receptors in the behavioral actions of methylxanthines. In the article, the authors correlated the behavioral excitation produced by theophylline in micromolar concentrations with the blockade of adenosine receptors.

Radulovacki reasoned that if the blocking of adenosine receptors produces excitation, then perhaps stimulation of the same receptors could induce sleep.[20] He knew that experiments by John Phillis and his group (Can. J. Physiol. Pharmacol. 57:1289-1312, 1979),[21] which utilized an iontophoretic application of adenosine in the brain, had demonstrated adenosine's depressant effect on the responses of neurons in several brain regions and that the general neurophysiological effects of adenosine were shown to be inhibitory. In addition, the preliminary experiments in dogs by Haulica et al. (J. Neurochem. 21:,1019–20, 1973)[22] and the administration of adenosine into the brains of rats, cats and fowl suggested that adenosine was able to produce behavioral sleep. The explanation of adenosine's hypnotic effect was through its interaction with serotonin, widely believed to be a sleep inducing agent. However, since there was no suggestion how this adenosine-serotonin link was achieved, experiments highlighting the potential role of adenosine in sleep had largely been forgotten.

Research collaboration with David W. Carley

In 1993, Radulovacki started a collaboration with David W. Carley, a Professor of Medicine, Bioengineering and Pharmacology at the UIC. Their research efforts focused on developing pharmacological approaches for the treatment of sleep apnea.[23] Since there were no medicines to alleviate this condition, Radulovacki and Carley set out to develop a drug treatment.[24] Their initial work focussed on an experimental model of sleep apnea in rats, initially testing the effects of adenosine compounds.[25] Eventually, they obtained positive results using serotonin and other compounds. As a result, the UIC patented their discoveries, obtaining numerous US and international patents.[26]

Patents for sleep and sleep-related disorders include:

  1. "Hypnotic Composition and Method of Inducing Sleep"; Inventor: Miodrag Radulovacki, US Patent 4537907, August 27, 1985. (This patent was issued to UIC before Radulovacki started his collaboration with Carley in 1993).[27]
  2. "Pharmacological Treatment for Sleep Apnea"; Inventors: Miodrag Radulovacki and David W. Carley, US Patent 6,331,536 B1, December 18, 2001.[28]
  3. "Neuropharmacological Treatments of Sleep-Related Breathing Disorders"; Inventors: Miodrag Radulovacki and David W. Carley, US Patent 6,555,564 B1, April 29, 2003.[29]
  4. "Pharmacological Treatment for Sleep Apnea"; Inventors: Miodrag Radulovacki and David W. Carley, US Patent 6,727,242 B2, April 27, 2004.[30]
  5. "Neuropharmacological Treatment of Sleep-Related Breathing Disorders"; Inventors: Miodrag Radulovacki and David W. Carley, US Patent 6,974,814 B2, December 13, 2005.[31]
  6. "Pharmacological Treatment for Sleep Apnea"; Inventors: Miodrag Radulovacki and David W. Carley, US Patent 7,160,898 B2, January 9, 2007.[32]
  7. "Method for Treating Sleep Apnea"; Inventors: David W. Carley and Miodrag Radulovacki, US Patent 7,705,039 B2, April 27, 2010.[33]
  8. "Methods for treating sleep disorders by cholecystokinin (CCK) receptor B antagonists": Inventors: David W. Carley and Miodrag Radulovacki, US Patent 8,053,413 B2, Nov. 8, 2011.[34]
  9. "Pharmacological treatments for sleep disorders (apnoe) with prostanoid receptor antagonists", Inventors: David W. Carley and Miodrag Radulovacki, US Patent 8,076,315, Dec. 13, 2011.[35]

Inventor of the Year 2010

Radulovacki was named the 2010 Inventor of the Year at the University of Illinois, alongside Carley. Radulovacki and Carley were honored by the University of Illinois for producing a dozen potential treatments for sleep apnea, many of which are now under consideration for commercial development.[36] Their results have culminated in an IllinoisVentures-supported start-up company, Pier Pharmaceuticals, that focuses on the treatment of obstructive sleep apnea.[37]

Membership in the Serbian Academy of Sciences and Arts

In October 2003, the Serbian Academy of Sciences and Arts in Belgrade elected Radulovacki as one of its Foreign Members for his significant scientific research contributions in the fields of Neuropharmacology, sleep disorders and sleep-related breathing disorders.

Yugoslav Student Summer Program

In 1990, Radulovacki initiated the Yugoslav Student Summer Program at the University of Illinois at Chicago (UIC) and the University of Illinois at Champaign-Urbana (UIUC) after the creation of International Linkage Agreements between the UIC and the Universities of Belgrade and Novi Sad in Yugoslavia.[38] The Yugoslav Student Summer Program lasted for 12 years and had 304 participants.[39]

Philanthropy

In 2005, Radulovacki established the Miodrag Radulovacki Family Prize for Excellence in Basic Sciences at the University of Illinois College of Medicine at Chicago. The purpose of the prize, given annually, is to honor a fourth year Medical student who displays a high degree of intellectual integrity and who has demonstrated strong academic achievement. The prize consists of a plaque and a check for $1,000.

Radulovacki made numerous contributions to his home town of Sremski Karlovci.

Personal life

Radulovacki lived in Chicago. He was a cross-country skier. He participated in several Birkebeiner-Kortelopet cross-country ski marathons in Cable-Hayward, Wisconsin. Radulovacki died on May 27, 2014, in Belgrade, Serbia, while on two-week trip to promote his philanthropic projects. He is survived by two sons (Brad Radulovacki and Branko Radulovacki) and four grandchildren (Grant, Katie, Reid and Ryan).[43] [44]

Selected publications

  1. 4705518 . 1973 . Radulovacki . M . 5-Hydroxyindoleacetic acid in cerebrospinal fluid: Measurements in wakefulness, slow-wave and paradoxical sleep . 50 . 2 . 484–8 . Brain Research . 10.1016/0006-8993(73)90757-9.
  2. 948760 . 1976 . Kovacević . R . Radulovacki . M . Monoamine changes in the brain of cats during slow-wave sleep . 193 . 4257 . 1025–7 . Science . 10.1126/science.948760. 1976Sci...193.1025K .
  3. 884510 . 1977 . Radulovacki . M . Buckingham . RL . Chen . EH . Kovacević . R . Similar effects of tryptophan and sleep on cisternal cerebrospinal fluid 5-hydroxyindoleacetic and homovanillic acids in cats . 129 . 2 . 371–4 . Brain Research . 10.1016/0006-8993(77)90018-X. 39245160 .
  4. 7417859 . 1980 . Radulovacki . M . Walovitch . R . Yanik . G . Caffeine produces REM sleep rebound in rats . 201 . 2 . 497–500 . Brain Research . 10.1016/0006-8993(80)91060-4. 8131652 .
  5. 7248800 . 1981 . Radulovacki . M . Zak . R . Amphetamine abolishes REM sleep rebound in rats: Effect of single injection . 217 . 2 . 420–4 . Brain Research . 10.1016/0006-8993(81)90022-6. 27030990 .
  6. 6694111 . 1984 . Radulovacki . M . Virus . RM . Djuricic-Nedelson . M . Green . RD . Adenosine analogs and sleep in rats . 228 . 2 . 268–74 . The Journal of Pharmacology and Experimental Therapeutics.
  7. 3916307 . 1985 . Radulovacki . M . Role of adenosine in sleep in rats . 5 . 3–4 . 327–39 . Reviews in Clinical & Basic Pharmacology.
  8. 15829175 . 2005 . Radulovacki . M . Adenosine sleep theory: How I postulated it . 27 . 2 . 137–8 . 10.1179/016164105X21814 . Neurological Research. 37526153 .
  9. 9542796 . 1998 . Radulovacki . M . Trbovic . SM . Carley . DW . Serotonin 5-HT3-receptor antagonist GR 38032F suppresses sleep apneas in rats . 21 . 2 . 131–6 . Sleep. 10.1093/sleep/21.2.131 . free .
  10. 10334159 . 1999 . Carley . DW . Radulovacki . M . Role of peripheral serotonin in the regulation of central sleep apneas in rats . 115 . 5 . 1397–401 . Chest . 10.1378/chest.115.5.1397.
  11. 20614859 . 2010 . Prasad . B . Radulovacki . M . Olopade . C . Herdegen . JJ . Logan . T . Carley . DW . Prospective trial of efficacy and safety of ondansetron and fluoxetine in patients with obstructive sleep apnea syndrome . 33 . 7 . 982–9 . 2894441 . Sleep. 10.1093/sleep/33.7.982 .

Related publications

Notes and References

  1. Web site: Faculty Research: Miodrag Radulovacki, MD, PhD Professor of Pharmacology and Medicine-Respiratory and Critical Care . University of Illinois College of Medicine.
  2. Radulovacki . Miodrag . Adenosine Sleep Theory: How I postulated it . Neurological Research . March 2005 . 27 . 137–138 . 10.1179/016164105X21814 . 2 . 15829175. 37526153 .
  3. Web site: Novel Drug Therapy for Sleep Apnea . University of Illinois at Chicago . . October 5, 2004.
  4. Web site: Faculty profile: Dr. David W. Carley . University of Illinois at Chicago.
  5. Web site: Meet the winners of the UIC 2010 Inventor of the Year Award . UIC News . February 10, 2011 . https://web.archive.org/web/20110507055836/http://innovations.uillinois.edu/features/2011-02-10/meet-winners-uic-2010-inventor-year-award . 2011-05-07.
  6. Web site: UIC OTM Announces 2010 Inventor of the Year . February 8, 2011 . UIC Office of Technology Management . dead . https://web.archive.org/web/20131021184237/http://otm.uic.edu/articles/2011-02-08/uic-otm-announces-2010-inventor-year . October 21, 2013 .
  7. Web site: Miodrag Radulovacki partial list of research publications, UIC Department of Pharmacology . PubMed.
  8. Web site: Miodrag Radulovacki, MD, PhD, Foreign Member . Serbian Academy of Sciences and Arts.
  9. http://www.medicine.uic.edu/UserFiles/Servers/Server_442934/File/medcomm/FY09%20Contributors%20Report_FINAL.pdf Summary biography of Miodrag Radulovacki, Illinois Medicine Fiscal Year 2009 Report - Honor Roll of Donors, page 27 (Prizing Discovery)
  10. http://www.uic.edu/nursing/CNSHR/NewFiles/radulovackiprofile.html University of Illinois, Dr. Miodrag Radulovacki profile
  11. http://www.gradprofiles.com/u-ill-chi-pharmacology.html University of Illinois Department of Pharmacology Faculty Profiles
  12. http://www.bri.ucla.edu/ UCLA Brain Research Institute
  13. Web site: In Memoriam: William Ross Adey, M.D., Professor of Anatomy and Physiology, Los Angeles, 1922–2004 . https://web.archive.org/web/20050929122113/http://www.universityofcalifornia.edu/senate/inmemoriam/williamrossadey.htm . dead . 2005-09-29 . John . Hanley .
  14. Book: Adey, W. Ross . W. Ross . Adey . Toshihiko . Tokizane . Structure and function of the limbic system . Hippocampal states and functional relations with corticosubcortical systems in attention and learning . 228–229 . Elsevier . https://books.google.com/books?id=Fi8OzS0HD3cC&pg=PA235 . 9780080861524 . 1967-01-01 .
  15. 1197913 . 1975 . Buckingham . RL . Radulovacki . M . The selective effects of alpha-methyl aromatic amino acids on brain monoamine metabolites and behavior in cats . 12 . 2 . 255–65 . Research Communications in Chemical Pathology and Pharmacology.
  16. From Amines to Sleep . Michel . Jouvet . Current Contents . March 22, 1993 . 8.
  17. News: Edward . Baumann . Klaus Unna, 79, U. Of I. Pharmacology Professor . . July 4, 1987.
  18. Adenosine analogs and sleep in rats . M. . Radulovacki . R. M. . Virus . M. . Djuricic-Nedelson . R. D. . Green . . February 1984 . 228 . 2 . 268–274. 6694111 .
  19. Adenosine receptors and behavioral actions of methylxanthines . S. H. . Snyder . J. J. . Katims . Z. . Annau . R. F. . Bruns . J. W. . Daly . . 78 . 5 . May 1981 . 3260–3264 . 10.1073/pnas.78.5.3260. 319541 . 6265942. 1981PNAS...78.3260S . free .
  20. Book: Radulovacki, Miodrag . Vladimir . Stefanovich . I. . Okyayuz-Baklouti . 1987 . Role of adenosine in cerebral metabolism and blood flow . Adenosine and sleep . 125–132 . 9067640980 . https://books.google.com/books?id=1McDQwLB6hMC&pg=PA125 .
  21. J. W. . Phillis . J. P. . Edstrom . G. K. . Kostopoulos . J. R. . Kirkpatrick . Effects of adenosine and adenine nucleotides on synaptic transmission in the cerebral cortex . . 1979 . 57 . 1289–1312 . 10.1139/y79-194. 93018 . 11, number 11.
  22. Preliminary data on the possible hypnogenic role of adenosine . Haulicǎ . I. . L. . Ababei . D. . Brǎnişlteanu . F. . Topoliceanu . Journal of Neurochemistry . 21 . 4 . 1019–1020 . October 1973 . 10.1111/j.1471-4159.1973.tb07549.x. 4754851 . 46663273 .
  23. Web site: Radulovacki Lab Research . University of Illinois at Chicago College of Medicine.
  24. Efficacy of mirtazapine in obstructive sleep apnea syndrome . Carley . D. W. . Olopade . C. . Ruigt . G. S. . Radulovacki . M. . Sleep . January 2007 . 30 . 35–41 . 17310863 . 1; number 1. 10.1093/sleep/30.1.35 . free .
  25. Book: Sleep-related Breathing Disorders: Experimental Models And Therapeutic Potential . David W. . Carley . Miodrag . Radulovacki . 9780824745684 . 2002-12-12. CRC Press .
  26. http://patent.ipexl.com/inventor/Miodrag_Radulovacki_1.html Patents by the UIC, Pharmacological Treatments for Sleep Disorders.
  27. http://patents.justia.com/1985/04537907.html "Hypnotic Composition and Method of Inducing Sleep"; Inventor: Miodrag Radulovacki.
  28. http://www.pharmcast.com/Patents/Yr2001/Dec2001/121801/6331536_Sleep121801.htm "Pharmacological Treatment for Sleep Apnea"; Inventors: Miodrag Radulovacki and David W. Carley.
  29. http://www.pharmcast.com/Patents/Yr2003/April2003/042903/6555564_Sleep042903.htm "Neuropharmacological Treatments of Sleep-Related Breathing Disorders"; Inventors: Miodrag Radulovacki and David W. Carley.
  30. http://patents.justia.com/2004/06727242.html "Pharmacological Treatment for Sleep Apnea"; Inventors: Miodrag Radulovacki and David W. Carley.
  31. http://patents.justia.com/2005/06974814.html "Neuropharmacological Treatment of Sleep-Related Breathing Disorders"; Inventors: Miodrag Radulovacki and David W. Carley.
  32. http://www.patentgenius.com/patent/7160898.html "Pharmacological Treatment for Sleep Apnea"; Inventors: Miodrag Radulovacki and David W. Carley.
  33. https://patents.google.com/patent/US7705039 "Method for Treating Sleep Apnea"; Inventors: David W. Carley and Miodrag Radulovacki.
  34. http://patent.ipexl.com/US/8053413.html "Methods for treating sleep disorders by cholecystokinin (CCK) receptor B antagonists": Inventors: David W. Carley and Miodrag Radulovacki.
  35. http://www.patentstorm.us/patents/8076315/claims.html "Pharmacological treatments for sleep disorders (apnoe) with prostanoid receptor antagonists": Inventors: David W. Carley and Miodrag Radulovacki.
  36. http://usaserbs.net/news-usa/170-serb-is-inventor-of-the-year-in-illinois.html UIC OTM Announces 2010 Inventor of the Year
  37. http://www.pierpharmaceuticals.com/ Pier Pharmaceuticals web site Home Page
  38. http://mir.cs.illinois.edu/uisp/english/introduction.html The Yugoslav Student Summer Program at the University of Illinois
  39. http://mir.cs.illinois.edu/uisp/english/participants.html Yugoslav Student Summer Program, Participants
  40. http://wikimapia.org/15049081/Hostel-ECO-CENTER, Ecological Center Karlovci
  41. http://www.ekoloskicentar.org/images/kuca/large/011.jpg Picture of renovated baroque facade of the Ecological Center in Karlovci, Ecological Center Karlovci web site
  42. http://www.ekoloskicentar.org/pgv/en/ Ecological Center Karlovci newsletter and update on the new construction project
  43. Web site: Miodrag Radulovacki Obituary . legacy.suntimes.com . 2023-07-05.
  44. Web site: Blic Online | Preminuo akademik Miodrag Radulovački . 6 February 2014 . Blic.rs . 2014-06-03.

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Miodrag Radulovacki".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2025, A B Cryer, All Rights Reserved. Cookie policy.