Receptor Binding affinity meaning and units

[dzaocom]

Hi. I've never learnt pharmacology but since I'm interested in it, I can't leave this topic unclear. Reading about cannabinoid receptor ligands, I messed up in binding affinities. As I know from internet, binding affinity is how strongly a particular substance binds to a receptor. Substances with higher affinity has stronger effects on receptor than lower ones, right? And the unit for binding affinity is nM which is a measure of concentration. For example substance with binding affinity of 1 nM has stronger effects than 0.1 nM right? Sometimes another molar unit micromole is used (i can't type that symbol of micro). Micromolar is much bigger than nanomolar so it should have higher affinity for receptors. But on the contrary, cannabonoid receptor substances that have binding affinity measured in nM are stronger than those measured in micromolar (for example 5 nM is stronger than 50 micromolar). Why it is so? Thanks

 

[Nagelfar]

Usually, the *lower* the Ki number, the more affinity; which is measured by the displacement of another (radiolabled for example) exogenous ligand.

check out the Wikipedia page list of cocaine analogues *click* and the more potent ones for serotonin have a lower number, with .05 being great affinity, and 10000.00 being effectively no affinity. etc.

 

[rabidrick]

For binding affinity people generally are referring to either the dissociation constant (the Kd value) or the association constant, Ka, which has no units. For your question why does it seem backwards, well Ka = 1/Kd. If units are given it is usually referring to Kd, the equilibrium dissociation constant (equilibrium referring to the binding and unbinding reactions).

Ki, or the inhibition constant, has to do with competitive binding assays and relates the ligand with the amount of competitor that displaces half of it (the IC50). Looking at that link it is giving the IC50 values it seems, so this would be referring to exactly that. Ki is an absolute value. Top make things even more complicated, when talking about potency it is often referring to the pIC50 value which is the negative log of the IC50 (log base ten).

FYI, for micro, u is fine (people should know what you are talking about).

 

[tryp2fun]

Hi. I've never learnt pharmacology but since I'm interested in it, I can't leave this topic unclear. Reading about cannabinoid receptor ligands, I messed up in binding affinities. As I know from internet, binding affinity is how strongly a particular substance binds to a receptor. Substances with higher affinity has stronger effects on receptor than lower ones, right? And the unit for binding affinity is nM which is a measure of concentration. For example substance with binding affinity of 1 nM has stronger effects than 0.1 nM right? Sometimes another molar unit micromole is used (i can't type that symbol of micro). Micromolar is much bigger than nanomolar so it should have higher affinity for receptors. But on the contrary, cannabonoid receptor substances that have binding affinity measured in nM are stronger than those measured in micromolar (for example 5 nM is stronger than 50 micromolar). Why it is so? Thanks

The affinity is measured by the concentration required to get 50% binding. If it is 5 nM for one compared to 50 uM for another, then it takes 10,000 times more ligand to get the same binding for the 50 uM compound as the 5 nM compound. However, the binding tells you nothing about the efficacy. The strongly bound compound could be a partial agonist and the weakly binding compound could be a full agonist, or vice versa. So, the 5 nM compound is stronger on a weight basis, but may not have stronger effects at equivalent doses.

 

[neurotic]

edit - nevermind

 

[dzaocom]

Thank you all!