Oxycodone works on what receptors? μ or κ

[tricomb]

Just read this on wikipedia.

Mechanism of action

A group of Australian researchers has proposed (based on a 1997 study in rats) that oxycodone, unlike morphine (the effect of which is mediated by μ-opioid receptors), acts on κ-opioid receptors.[18] Further research by this group indicates the drug appears to be a κ2b-opioid agonist.[19] However, this has been disputed, primarily on the basis that oxycodone produces effects typical of μ-opioid agonists.[20]

Research by a Japanese group suggests that the effect of oxycodone is mediated by different receptors in different situations. Specifically, in diabetic mice the κ-opioid receptor appears to be involved in the antinociceptive effects of oxycodone,[21] while in non-diabetic mice the μ1-opioid receptor seems to be primarily responsible for these effects.[22]

This is interesting, I always thought oxycodone was a μ-opioid agonist. What are your thoughts?

 

[sekio]

It probably activates both, but mu primarily.

Also I'd wager it activates delta OR too. My money's on it having the lowest ec50 at mu.

 

[mgrady3]

there's not one clear answer to your question except for both -
oxycodone certainly has affinities for various opioid receptors. I can't comment specific numbers but I'd reckon Sekio was right in that mu having the lowest ec50.

from drugbank.ca :

Oxycodone acts as a weak agonist at mu, kappa, and delta opioid receptors within the central nervous system (CNS). Oxycodone primarily affects mu-type opioid receptors, which are coupled with G-protein receptors and function as modulators, both positive and negative, of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine, and noradrenaline is inhibited. Opioids such as oxycodone also inhibit the release of vasopressin, somatostatin, insulin, and glucagon. Opioids close N-type voltage-operated calcium channels (kappa-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (mu and delta receptor agonist). This results in hyperpolarization and reduced neuronal excitability.

http://www.drugbank.ca/drugs/DB00497

CLINICAL AND TRANSLATIONAL ONCOLOGY
Volume 9, Number 5, 298-307, DOI: 10.1007/s12094-007-0057-9

Oxycodone is a semi-synthetic opioid with an agonist activity on mu, kappa and delta receptors. Equivalence with regard to morphine is 1:2. Its effect commences one hour after administration and lasts for 12 h in the controlled-release formulation. ......

Oxycodone has the same mechanism of action as other opioids: binding to a receptor, inhibition of adenylyl-cyclase and hyperpolarisation of neurons, and decreased excitability. These mechanisms also play a part in the onset of dependence and tolerance.

http://www.springerlink.com/content/46353182k028275k/

 

[Hammilton]

How'd that make it to Wikipedia? I'm not going to look into it, but I'd wager that either the studies were badly done or are overstating the difference in responsibility the two receptors have for various effects.