However, despite the greater in vitro activity of some of its metabolites, it has been determined that oxycodone itself is responsible for 83.0% and 94.8% of its analgesic effect following oral and intravenous administration, respectively. Oxymorphone plays only a minor role, being responsible for 15.8% and 4.5% of the analgesic effect of oxycodone after oral and intravenous administration, respectively. Although the CYP2D6 genotype and the route of administration result in differential rates of oxymorphone formation, the unchanged parent compound remains the major contributor to the overall analgesic effect of oxycodone. In contrast to oxycodone and oxymorphone, noroxycodone and noroxymorphone, while also potent MOR agonists, poorly cross the blood–brain barrier into the central nervous system, and for this reason are only minimally analgesic in comparison. κ-opioid receptor
In 1997, a group of Australian researchers proposed (based on a study in rats) that oxycodone acts on KORs, unlike morphine, which acts upon MORs. Further research by this group indicated the drug appears to be a high-affinity κ2b-opioid receptor agonist. However, this conclusion has been disputed, primarily on the basis that oxycodone produces effects that are typical of MOR agonists. In 2006, research by a Japanese group suggested the effect of oxycodone is mediated by different receptors in different situations. Specifically in diabetic mice, the KOR appears to be involved in the antinociceptive effects of oxycodone, while in nondiabetic mice, the μ1-opioid receptor seems to be primarily responsible for these effects. Pharmacokinetics
Instant-release absorption profile
Oxycodone can be administered orally, intranasally, via intravenous, intramuscular, or subcutaneous injection, or rectally.
The loss of other genes in the deleted region may help explain why the features of Smith–Magenis syndrome vary among affected individuals. A small percentage of people with Smith–Magenis syndrome have a mutation in the RAI1 gene instead of a chromosomal deletion. These deletions and mutations lead to the production of an abnormal or nonfunctional version of the RAI1 protein. RAI1 is a transcription factor that regulates the expression of multiple genes, including several that are involved in controlling circadian rhythm, such as CLOCK. The groups led by James Lupski (Baylor College of Medicine) and Sarah Elsea (Virginia Commonwealth University) are in the process of studying the exact function of this gene in relation to Smith Magenis Syndrome.SMS is typically not inherited. This condition usually results from a genetic change that occurs during the formation of reproductive cells (eggs or sperm) or in early fetal development. People with Smith–Magenis syndrome most often have no history of the condition in their family. Diagnosis
SMS is usually confirmed by blood tests called chromosome (cytogenetic) analysis and utilize a technique called FISH (fluorescent in situ hybridization). The characteristic  micro-deletion was sometimes overlooked in a standard FISH test, leading to a number of people with the symptoms of SMS with negative results. The recent development of the FISH for 17p11.2 deletion test has allowed more accurate detection of this deletion. However, further testing is required for variations of Smith–Magenis syndrome that are caused by a mutation of the RAI1 gene as opposed to a deletion.