What is Affinity?

[King-Anubis]

Hey everyone,

I Have a passing interest in pharmacology, but one thing I've never understood properly is what affinity is. I see it referenced commonly and was hoping someone could give me a brief explanation, with the knowledge that I don't have a background in biology or chemistry - rather mathematics and physics :S

Hopefully I don't sound too dumb, but from what I can gather the higher the affinity of a substance the stronger it binds to a given receptor. But does a substance with a higher affinity provoke a stronger response from the aformentioned receptor?

Furthermore, if this is the case, can a substance with a higher affinity 'displace' one with a lower affinity? For example... if substance A has a lower affinity then substance B, then would substance B displace substance A? I guess I could use the comparison of codeine and morphine (Substance A and B respectively). If I took codeine, which would bind to my opiate receptors, would taking morphine then displace codeine or just bind to free receptors?

Thanks in advance!

 

[darthrhonin]

From what i know, the more substance A has affinity for receptor , the less dosage you have to take to feel a certain effect
But i don't think affinity influence the displacement, i would talk about competitivity in that case
But note, if you use a substance with higher affinity, you need less free receptors, because it take a small amount of substance to activate the right ones

 

[King-Anubis]

Ah okay I think I understand now. The higher a substance's affinity for a receptor the more likely it is to bind to it?

 

[darthrhonin]

yes sir, that's right
and the lesser amount you need to produce effects

 

[polymath]

From high school chemistry you might be familiar with the concept of an equilibrium constant for a chemical reaction: see http://en.wikipedia.org/wiki/Equilibrium_constant .

What is called affinity is just the eq. constant for the reaction: L + R --> LR ,

where L is the ligand (drug molecule), R is the receptor, and LR is a receptor with ligand bound to it.

When the affinity is a large number, a small concentration of the drug in body fluids is enough to occupy a significant fraction of receptors it binds to. Therefore high affinity usually means smaller effective dose.

Effective dose also depends on the bioavailability, metabolic rate and distribution kinetics of the drug, though.

 

[endotropic]

is this true ? i was thinking the effect of a drug is measured in IC50 and EC50, while the affinity just says how easy a drug attaches to a receptor. antagonists have high affinity and produce no effect.

If you're comparing two drugs with equal efficacy then you can compare doses using affinity, assuming that they're producing effects at the same receptor. For example you could compare the affinities of two full agonists at the mu opiate receptor and predict the relative doses pretty accurately. If you want to compare a full agonist with a partial agonist you can't use affinity values to predict drug effect, in that case you need to compare EC50.

In either case using EC50 is the most accurate measure, but when comparing drugs with similar efficacy you can cheat and use affinity values.