Pharmaceutical question: receptor binding affinities table - how to read it??

[NoLiver]

I found this table on the Wiki page of a chemical substance and i think its about receptor bindings. It's interesting because of the big variety of binding sites.

But i still don't know how powerful the substance will affect the individual types of receptors and transporter proteins listed on the left column. Because im not able to understand the meaning of the values in the right column.

What are the abbreviations "pKi & SEM" for? And how to get useful information about the pharmaceutical effects of the substance out of this table? (At least theoretically).
There are no Informations exactly like these about that rc in my native language.

Could someone explain that to me?
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By the way: it's about 5-MeO-DALT, but who cares... not a controlled substance in my country, yet. Will broach it in another thread, if i find one.

Greetz

 

[serotonin2A]

Ki is the dissociation constant. It measures the affinity of the drug for a receptor. You can think of the Ki as the concentration where 50% of the receptor population will be occupied by the drug. So if you have two Ki values and one is higher, the drug has higher affinity for the site with the lower Ki (because binding requires a lower concentration of the drug).

To make it easier to compare multiple Ki values at the same time, they are sometimes given as the pKi, which is the negative log of the Ki. For pKi, affinity increases as the value increases. The pKi is a useful way to compare affinity values based on how many orders of magnitude they are different (because binding occurs on a log scale, not a linear scale). So if two pKi values are (for example) 8.5 and 9.5, then you know there is an order of magnitude (ie, 10-fold) difference between the values.

Giving affinity values as log values allows you to easily compare selectivity. If the difference between pKi values is >2, then it means the drug has some selectivity for the site with the higher pKi. The intensity of a drug effect is determined by how many receptors are occupied, and so a difference of 2 between pKi values can be equivalent (as an example) to going from about 10% to about 90% occupation.

TL/DR: Higher pKi values mean higher affinity binding to the site.

The values for 5-MeO-DALT are typical for tryptamine hallucinogens. They usually have the highest affinity for serotonin receptors, alpha2 adrenergic receptors, sigma sites, and the serotonin transporter (SERT).

 

[aced126]

Ki is the dissociation constant. It measures the affinity of the drug for a receptor. You can think of the Ki as the concentration where 50% of the receptor population will be occupied by the drug. So if you have two Ki values and one is higher, the drug has higher affinity for the site with the lower Ki (because binding requires a lower concentration of the drug).

To make it easier to compare multiple Ki values at the same time, they are sometimes given as the pKi, which is the negative log of the Ki. For pKi, affinity increases as the value increases. The pKi is a useful way to compare affinity values based on how many orders of magnitude they are different (because binding occurs on a log scale, not a linear scale). So if two pKi values are (for example) 8.5 and 9.5, then you know there is an order of magnitude (ie, 10-fold) difference between the values.

Giving affinity values as log values allows you to easily compare selectivity. If the difference between pKi values is >2, then it means the drug has some selectivity for the site with the higher pKi. The intensity of a drug effect is determined by how many receptors are occupied, and so a difference of 2 between pKi values can be equivalent (as an example) to going from about 10% to about 90% occupation.

TL/DR: Higher pKi values mean higher affinity binding to the site.

OP. yep, it's a bit like changing [H+] values to pH values in chemistry, so that comparisons can be made quickly and easily.

 

[sekio]

Please do remember that Ki is way more relevant to measuring drugs activity in a petri dish, it doesn't take into account absorbtion, distribution, metabolism etc.