Miodrag (Misha) Radulovacki (Serbian: Миодраг Радуловачки, 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), Radulovacki's research accomplishments include: (1) the Adenosine Sleep Theory, and (2) pioneering pharmacological studies for the treatment of sleep apnea, together with research collaborator, David W. Carley, (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." Radulovacki published more than 170 scientific papers. Radulovacki was also a Foreign Member of the Serbian Academy of Sciences and Arts.
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. 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 where his mentor was Ross Adey. 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. 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. This approach was of interest since Michel Jouvet's Monoamine Theory of Sleep, 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 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). 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) 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. He knew that experiments by John Phillis and his group (Can. J. Physiol. Pharmacol. 57:1289-1312, 1979), 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) 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. Since there were no medicines to alleviate this condition, Radulovacki and Carley set out to develop a drug treatment. Their initial work focussed on an experimental model of sleep apnea in rats, initially testing the effects of adenosine compounds. Eventually, they obtained positive results using serotonin and other compounds. As a result, the UIC patented their discoveries, obtaining numerous US and international patents. Patents for sleep and sleep-related disorders include:
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