1. Glasgow Caledonian University 2. Glasgow Caledonian University 3. Glasgow Caledonian University 4. Glasgow Caledonian University
Oxycodone is a semisynthetic opioid and a narcotic analgesic which is usually used in the management of moderate to severe pain. its mode of action is still a controversy. some researchers believe the anti-nociceptive effects of oxycodone are κ mediated while others consider μ-receptor as the major receptor mediating its effects. there are four separate opioid receptors , dor-1 (encoding a δ receptor), mor-1 (encoding a μ receptor), kor-1 (encoding a κ receptor) and the fourth member kor-3 or orl-1. the aim of this study was to investigate the mechanism of action of oxycodone and the receptors mediating its effects in guinea pig ileum under experimental conditions.
The isolated tissue bioassay experiment using guinea pig myenteric plexus longitudinal muscle preparation was used and the effects of selective μ-receptor agonist (damgo) and antagonist (ctap) and selective κ-receptor agonist (u69, 593) and antagonist (nor-bni) along with a non-selective antagonist (naloxone) were observed and compared to those of oxycodone. the mplm tissue was set up in an organ bath containing krebs solution at a temperature of 37 celsius and the aeration ratio of 95:5 of oxygen and carbon dioxide. the tissue was then stimulated using an isometric transducer and the responses were recorded using powerlab recording system. crc for each drug was created and compared.
ctap at 100nm concentration did not have any effect on damgo and oxycodone crc but at 1μm concentration produced a statistically significant rightward shift but no effect on u69, 593 crc. naloxone was used at two different concentrations, 10 and 100nm, and they produced almost the same rightward shift of the damgo crc and exactly the same shift of the u69, 593 crc and in case of oxycodone naloxone 10nm produced a significant rightward shift of the oxycodone crc. nor-bni had no effect on damgo and oxycodone, no shift of the crc curve, but it produced more rightward shift (almost 2 log unit shift) of the u69, 593 crc which indicates nor-bni`s high affinity for kappa receptor.
Damgo and oxycodone have lower affinity for kappa receptor and oxycodone is more likely to act on μ-receptor and exhibits its anti-nociceptive effects through μ-receptor than κ-receptor. based on the obtained results and the observations made, it is possible to conclude that oxycodone exhibits its anti-nociceptive effects through μ-receptors than other opioid receptors.however, as the number of the experiments carried out was not high enough to allow us to draw a definite conclusion, these experiments therefore cannot be fully relied on and the need for further studies to establish the true mechanism of action of oxycodone is indicated.
Oxycodone, opioid receptors, isolated tissue bioassay, selective/nonselective agonists and antagonis