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: • "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). • "Pharmacological Treatment for Sleep Apnea"; Inventors: Miodrag Radulovacki and David W. Carley, US Patent 6,331,536 B1, December 18, 2001. • "Neuropharmacological Treatments of Sleep-Related Breathing Disorders"; Inventors: Miodrag Radulovacki and David W. Carley, US Patent 6,555,564 B1, April 29, 2003. • "Pharmacological Treatment for Sleep Apnea"; Inventors: Miodrag Radulovacki and David W. Carley, US Patent 6,727,242 B2, April 27, 2004. • "Neuropharmacological Treatment of Sleep-Related Breathing Disorders"; Inventors: Miodrag Radulovacki and David W. Carley, US Patent 6,974,814 B2, December 13, 2005. • "Pharmacological Treatment for Sleep Apnea"; Inventors: Miodrag Radulovacki and David W. Carley, US Patent 7,160,898 B2, January 9, 2007. • "Method for Treating Sleep Apnea"; Inventors: David W. Carley and Miodrag Radulovacki, US Patent 7,705,039 B2, April 27, 2010. • "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. • "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.
Inventor of the Year 2010 Radulovacki was named the 2010 Inventor of the Year at the University of Illinois, alongside Carley. Their results have culminated in an IllinoisVentures-supported start-up company, Pier Pharmaceuticals, that focuses on the treatment of obstructive sleep apnea.
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==