Opiates/Opioids' affinity for each receptor, μ κ δ Lets build a table/chart!!!!

Opiates/Opioids' affinity for each receptor, μ κ δ Lets build a table/chart!!!!

There are many opiate users, and there are many opiates and opioids too.
There are three main Opioid receptors, each with its different effect, a little summary could be:

- μ - Mu = Analgesia, Euphoria, Sedation, Miosis, Respiratory Depression, Costipation

- κ - Kappa =Perceptual Distortions, Dysphoria, Analgesia, Psychedelia/Delirium/Dissociation, Miosis

- δ - Delta =Antidepressant Effect, Analgesia, Convulsions

Every opioid will have some degree of affinity for some of these receptors and the effect it gives will depend onto which receptor it has affinity, how much affinity it has for each receptor, the fact if it is an Agonist, a Partial Agonist, an Antagonist or an Inverse Agonist and its Intrinsic Activity(Efficacy) in case it is a PA.

The most used opiate in the world is Heroin, which actually seems just to be a pro-drug to the long known Morphine, then there are the two most used opioids for the treatment of Heroin addiction, Methadone and Buprenorphine. It would be nice to know also the different affinities to each receptor of the two main used opioid antagonists, Naloxone and Naltrexone.
I would like to make a table with the different affinities and activities of the opioid i mentioned (you can suggest other ones if you have data), sadly i cant have access to full articles on academic websites for the moment, i only have access to abstracts, with usually don't contain much quantitative data.

HERE IS WHERE YOU CAN HELP! Suggest and write in your posts the different affinities and activities of these opioid to each receptor, i will edit my post to add your data in the chart that i will make here in the first post to be well visible to anyone who open this thread!

Edit: "When i put (-) or (+) after a substance called "Antagonist" it is to clarify if said chemical at that receptor behaves as a very low Efficacy partial agonist: (+), or as a very low Efficacy inverse agonist. If instead i put this symbol (0) it means the substance is believed to be a true Silent Antagonist or its antagonistic properties are not specified. As i'm starting to realize that terms like "Silent Antagonist" or "Full Agonist" are only great approximations, we can only put our best to make Science closer to Common Sense and Understanding of Life."



MORPHINE (HEROIN)

- μ - Mu = Affinity: 4.55nM Activity: Agonist, Efficacy: 75%

- κ - Kappa = Affinity: 26.9nM Activity: Agonist

- δ - Delta = Affinity: 217nM Activity: Agonist


METHADONE

- μ - Mu = Affinity: 3.16nM Activity: Agonist, Efficacy: 77%

- κ - Kappa = Affinity: ≈500/1'000nM aka Negligible Effect

- δ - Delta = Affinity: ≈500/1'000nM aka Negligible Effect


BUPRENORPHINE

- μ - Mu = Affinity: 0.9nM Activity: Partial Agonist, Efficacy: 34%

- κ - Kappa = Affinity: 0.71nM Activity: Antagonist (0)

- δ - Delta = Affinity: 3.7nM Activity: Antagonist (+)


NALOXONE

- μ - Mu = Affinity: 1.2nM Activity: Antagonist (-)

- κ - Kappa = Affinity: 12nM Activity: Antagonist (-)

- δ - Delta = Affinity: 19nM Activity: Antagonist (-)


NALTREXONE

- μ - Mu = Affinity: 0.39nM Activity: Antagonist (-)

- κ - Kappa = Affinity: 1.75nM Activity: Antagonist (-)

- δ - Delta = Affinity: 26.6nM Activity: Antagonist (-)


CODEINE

- μ - Mu = Affinity: 105nM Activity: Agonist

- κ - Kappa = Affinity: 15000nM Activity: Agonist

- δ - Delta = Affinity: 9300nM Activity: Agonist


OXYCODONE

- μ - Mu = Affinity: ≈23.4nM Activity: Agonist

- κ - Kappa = Affinity: ≈1560nM Activity: Agonist

- δ - Delta = Affinity: ≈982nM Activity: Agonist

PDSP is your friend...

e.g. buprenorphine - http://pdsp.med.unc.edu/pdsp.php?kn...=&KiLess=&kiAllRadio=all&doQuery=Submit+Query

wow, my friend you are!!! Thankz!

I can edit the image into your post if you want.

Ektor said:

There are many opiate users, and there are many opiates and opioids too.
There are three main Opioid receptors, each with its different effect, a little summary could be:

- μ - Mu = Analgesia, Euphoria, Sedation, Miosis, Respiratory Depression, Costipation

- κ - Kappa =Perceptual Distortions, Dysphoria, Analgesia, Psychedelia/Delirium/Dissociation, Miosis

- δ - Delta =Antidepressant Effect, Analgesia, Convulsions

Click to expand...

Don't forget NOP (aka ORL1): nociceptin opiate receptor

I know about the nociceptin receptor but, as this receptor is pretty poorly understood, and we dont know so well agonist and antagonist to that receptor.
I prefered not to add that one and leave this paper yes, advanced, but not overly confusing to the people who want to learn their first bits of psychopharmacology.

No offense man, i greatly appreciate any input and suggestion!!!
THANKS TO EVERYONE!

Hey Epsilon, dunno if you recieved my PM but, what do you mean by "I can edit the image into your post if you want." ?

I would like it more image like, but i like it also able to be modified if needed. that was my point.

I would love if you transform it into something good looking!!!! =)

Thanks so much!!!!!!!

I finally completed the chart, you should take this data as something indicative and not for sure precise, it has however been collected strictly from scientific papers with binding assays, efficacy comparisons and things like that. Sometimes, when data was confused and discordant i personally had to compute the average, in the most scientifically minded manner i could (Chemistry technical high school helped ).

I hope this data table could be useful to all of you and could it offer inspiration for new good ideas to make this world a better place, THANKS TO EVERY ONE OF YOU!!!


CONNECTION IS THE KEY!!!!!!! =)

Some more binding affinities:

Codeine:
IC50 Mu - Human 105 nM (Source: http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=150822)
IC50 Delta - Human: 9300 nM (Source: http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=148090)
IC50 Kappa - Human? 15000 nM (Source:http://www.bindingdb.org/data/mols/tenK5001/MolStructure_50019351.html)

Hydrocodone
Ki Mu - Rat 19.8nM (Source:http://www.ncbi.nlm.nih.gov/pubmed/1
Ki Kappa ?
Ki Delta ?

Oxycodone
Ki Mu - Rat 43.6 nM (Source:http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=239148)
Ki Delta - Rat 1087 nM (Source:http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=239360)
Ki Kappa - Rat 2658nM (Source: http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=239148)

I'll try find some more binding values later. I'm a bit sleep deprived at the moment, and my Dexies are starting to wear off which means I lack the fuel to trawl through journals

Thanks a lot Serotonergic, i will enter your data about Codeine and Oxycodone in the chart as they are more complete than hydro, at least we have their Mu/Kappa/Delta proportion, which is the mean purpose of this thread.
We could enter Hydrocodone when we will have its Affinity values complete. Nevermind about Efficacy/intrinsic activity values, they are so rare! and only available for the most used/known opioids or the ones (like Bupe) which have a particular mode of action.

:D

Bum bum!!

Edit: I made an average for the Oxy between the values you brought and other values i gathered from other medical web platforms, the results could be not so precise, so remember that oxy has pretty big approximations in its values.

Generally I've used values which use 3H-DAMGO as the radioligand for displacement @ Mu.

Various non-opiate opioids

Levorphanol (l-Morphan)
Mu: 0.21 nM Ki (http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=362196)
Kappa 2.3 nM Ki (http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=290257)
Delta 4.2 nM Ki (http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=259395)

Dextropropoxyphene (Darvon)
(Source: Ki Database)
Mu: 34.500 nM Ki
Kappa: 1220 nM Ki
Delta 380 nM Ki

Methadone
Source: Ki Database
Mu: 5.6 nM (average) Ki
Kappa 1000 nM Ki
Delta 1000 nM Ki

Tramadol
Source: Ki Database
Mu: 2120 nM Ki (rat)
Kappa >10000 nM Ki (rat) (negligible affinity)
Delta >10000 nM Ki (rat) (negligible affinity)
There were some human values that indicated substantially lower affinities for kappa and delta but the test ligands were undefined and the values seemed inconsistent and odd

O-Desmethyltramadol(Tramadol's active metabolite responsible for its opioid activity
Source: Ki Database
Mu: 8.6 nM Ki (human)
Kappa 450 nM Ki (human)
Delta 2900 nM Ki (human)

Merperidine/Pethidine
Mu: 315 nM (IC50) (human) (source:http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=152239)
Kappa 2370 nM (IC50) (source:http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=147859)
Delta 10 000 nM (IC50) (source:http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=148078)

Some more opiates

Oxymorphone (Opana)
Source: Ki Database
Mu: 0.97 nM (Ki) (rat)
Kappa: 61.6 nM (Ki) (rat)
Delta 80.5 nM (Ki) (Rat)

Hydromorphone (Dilaudid)
Source: Ki Database
Mu: 0.28 nM (Ki) (Human)
Kappa: 2.8 nM (Ki) (Human)
Delta 38.0 nM (Ki) (Human)

Hydrocodone
Source:Ki database
Mu: 11.1 nM (Ki) (Rat)
Kappa 501.0 nM (Ki) (Rat)
Delta 962.0 nM (Ki) (Rat)

Dihydrocodeine
Source
Mu: 352 [+/- 12] nM (Ki) (Guinea pig)
Kappa: 14242 [+/- 466] nM (Ki) (Guinea pig)
Delta: 5905 [+/- 359] (Ki) (Guinea pig)

Kratom Alkaloids!
Source:http://mitizane.ll.chiba-u.jp/metadb/up/assist1/Y2006-17.pdf

Not sure if i calculated them from pKi correctly. I just did (10^-[pKi]) x 10^9

7-Hydroxymitragynine
Mu: 9.78 nM
Kappa 195 nM
Delta: 144.5 nM

9-hydroxycorynatheidine
Mu: 12.0 nM
Kappa 2951 nM
Delta >10000 nM (negligible)

You know you can draw tables in the advanced posting mode? Slightly more work but easier to compare.

Transform said:

You know you can draw tables in the advanced posting mode? Slightly more work but easier to compare.

Click to expand...

Oh i didnt know! Thanks transform, i will figure out what to do with all this data as soon as i will have some time and energy!!


Edit: OH HELL! Serotonergic, i didnt see the enormous amount of data you just brought, thankz! I will soon be workin with all this!!!!

Could Kratom be classified at all on this chart?

No, it has a variable balance of alkaloids depending on species and cultivar, growing/storage conditions, etc

But, couldn't those specific alkaloids be accounted for on here? I've never come across anything, but perhaps someone has for 7-hydroxymitragynine...

Read SerotonergicHaze's post, he already mentioned them

Wow... :-/

Is there a way to create a table with all the affinities and activities of all these opioids that COULD BE EDITED BY ANYONE who has quality data?

Someone could transcribe it to a wiki somewhere. If other people post more data I will tkink about transcribing it to a pretty table on the BL Wiki.