• Neuroscience & Pharmacology Discussion Welcome Guest
    Posting Rules Bluelight Rules
    Recent Journal Articles Chemistry Mega-Thread
    FREE Chemistry Databases! Self-Education Guide

  • N&PD Moderators: Skorpio | someguyontheinternet

Post your drug binding/affinity/efficacy tables

negrogesic

negrogesic

Moderator: BDD, OD
Staff member
Joined
Jul 21, 2002
Messages
12,556
Location
Negronesia
I wish there was some sort of repository that had tables for all different classes of ligands with their known ki/ec50/ic50 values. None exist as far as i know. I once made a spreadsheet of all manners of drugs and their affinities for various targets but i lost it years ago.

In any event I'll get this drug nerd party started:


 
Looks like they made an error in table 1, they have dextro and levo methamphetamine ec50s reversed.
 
Is there anything in these numbers that indicate the preferential level binding between different substances and a receptor when one substances is already bound to the receptor? These values relate to isolated binding propensity, in the absence of any competing substance right?

Different substances do bind competeitively, but the ki value presumes the receptor is vacant at the time right?
 
Perforated said:
Is there anything in these numbers that indicate the preferential level binding between different substances and a receptor when one substances is already bound to the receptor? These values relate to isolated binding propensity, in the absence of any competing substance right?

Different substances do bind competeitively, but the ki value presumes the receptor is vacant at the time right?
Click to expand...

Yes the measurements are calculated in the absence of a competing ligand.

But there is a difference between affinity and efficacy, for instance buprenorphine has very high affinity for the MOR and comparatively low efficacy, so its able to block the effects of lower affinity opioids that are yet far more effective in activating the receptor (like morphine). These are like keys. Buprenorphine for the most part has an excellent fit, and as such has very high affinity (as does its ultra potent full agonist relative etorphine) but it has a pesky little cyclopropyl group sticking out the side that makes it unable to fully activate the MOR. Its like an almost perfect key with a burr on the side that fits really well but makes its a pain in the ass when you try to turn it to a certain point.
 
Thanks. That makes sense. I was thinking also of the case with LSD which has a very high affinity (low ki) for 5HTP2 receptors but also a high efficacy because it has an extracellular loop that forms a lid over the diethylamide end of the binding cavity making it difficult to unbind or be dislodged thus leading to long duration of trips?

I was also curious if these properties influence or help predict the subjective effect of drug combinations depending on which order you take the drugs. For example meth followed by LSD vs LSD followed by meth. In equivalent amounts the former seems to greatly reduce any depersonalisation while the latter does not necessarily stop depersonalisation.
 
For instance, tables like this:



Years ago i put together a table for opioids in a similar format but lost it. It was far more extensive than this one.
 
Yes the measurements are calculated in the absence of a competing ligand.
Click to expand...

I thought that Ki was usually calculated by measuring how effectively a ligand displaces some other compound from the receptor... i.e. radiolabeled [3H]dopamine for dopamine receptors ?
 
sekio said:
I thought that Ki was usually calculated by measuring how effectively a ligand displaces some other compound from the receptor... i.e. radiolabeled [3H]dopamine for dopamine receptors ?
Click to expand...

Yeah the standard competition assay (thus the term inhibition constant) though I would imagine there may be newer approaches. I think he was asking if two other ligands were tested at the same time against whatever they using (for instance DAMGO)
 
just found this short summary of benzodiazepine affinities:


triazolam 1.31 umol
alprazolam 1.38 umol
clonazepam 1.43 umol
flunitrazepam 1.60 umol
lorazepam 2.65 umol
loprazolam 2.90 umol
lormetazepam 3.58 umol
eszopiclone 4.24 umol
estazolam 4.73 umol
bromazepam 14.61 umol
quazepam 17.06 umol
zaleplon 19.65 umol
zopiclone 21.22 umol
nitrazepam 30.48 umol
diazepam 32.67 umol
medazepam 33.23 umol
nordazepam 33.25 umol
clorazepate 41.27 umol
prazepam 41.56 umol
flurazepam 47.08 umol
halazepam 51.03 umol
ketazolam 53.69 umol
clobazam 59.90 umol
zolpidem 59.90 umol
temazepam 63.90 umol
oxazepam 67.00 umol
chlordiazepoxide 75.00 umol
 
izo said:
just found this short summary of benzodiazepine affinities:


triazolam 1.31 umol
alprazolam 1.38 umol
clonazepam 1.43 umol
flunitrazepam 1.60 umol
lorazepam 2.65 umol
loprazolam 2.90 umol
lormetazepam 3.58 umol
eszopiclone 4.24 umol
estazolam 4.73 umol
bromazepam 14.61 umol
quazepam 17.06 umol
zaleplon 19.65 umol
zopiclone 21.22 umol
nitrazepam 30.48 umol
diazepam 32.67 umol
medazepam 33.23 umol
nordazepam 33.25 umol
clorazepate 41.27 umol
prazepam 41.56 umol
flurazepam 47.08 umol
halazepam 51.03 umol
ketazolam 53.69 umol
clobazam 59.90 umol
zolpidem 59.90 umol
temazepam 63.90 umol
oxazepam 67.00 umol
chlordiazepoxide 75.00 umol
Click to expand...

Looks more like equivalency figures (blood concentrations that produce equivalent effects) than binding figures, but hey ill take it (I've never this before).

Must be blood concentrations that produce equivalent antiseizure effects or who knows, because in terms of hypnotic effects one wouldn't think you'd need twice the concentration or zolpidem relative to diazepam in that regard. Muscle relaxant properties are pretty weak though. I wonder on what metrics (drug effects) they are basing equivalency with these numbers
 
I hope these images stay live for a long time because i find myself coming back to this thread to reference these tables. What can i say, i guess i am a bit of a drug nerd, i enjoy reading these tables and examining the ratios/selectivity of the various compounds. Would love to compile all these in a spreadsheet one day again (I've done it once before but lost the file).

This is interesting, I've never seen these:



 
I just want to point out that comparing Ki between different experiments is not valid. I'm sure everybody here knows but just an important point when do much data is being presented together. This is a wonderful research for armchair pharm tho bigups to everybody submitting data.
 
You must log in or register to reply here.
Top