Can someone explain this binding affinity profile please (and in general)

[Berdo tm1]

http://en.wikipedia.org/wiki/Reboxetine#Pharmacology

I dont get it totally still but comparing a few different charts it seemed that the lower the number is the more it affects that neurotransmitter is that correct?

Im still confused tho cos i read reboxetine mainly affects alpha 1 but using what i said above this would not be true.

So could someone please explain both the chart above and also generally how one untangles the numbers in these charts.

Cheers.

 

[adder]

In layman's words, for Ki, the lower the number, the higher the affinity. That is the lower the number, the less of a compound is needed to exert an effect. Ki > 10'000 nM means that reboxetine didn't have an effect at a tested site at 10'000 nM. It is inactive there, especially when the compound is active at 13.4 nM as a NET inhibitor. It also is an active SERT inhibitor, but the affinity for SERT is over 20 times lower, so you can say that it is a fairly selective NET inhibitor (you'd need a twenty times higher dose of reboxetine for it to have a similar action at SERT - the active dose for SERT inhibition would be so high that you'd already have a lot of side effects coming from NET inhibition). Also, the affinities for 5-HT(2C) receptors and H1 receptors are low enough to say that they don't play an important role in reboxetine's pharmacodynamics at doses which are enough to effectively block NET.

 

[Berdo tm1]

Ok thanks. So what is the deal with there being both NET and also a1 and a2? Are these each distinct with their own form of effects? SAme with SERT and ht2 etc? and d2/3 are all to be considered seperate entities unto themselves?

 

[sekio]

All of those are seperate receptors, yeah. NET is the norepinephrine transporter, a1/a2 are postsynaptic adrenergic receptors, etc.

There's lots of targets that antidepressants/antipsychotics hit in the brain. All of them are different and contribute to the unique profile of each medication.

 

[Berdo tm1]

ok cheers. i wasnt sure if they were related- ie if the NET pushed it thru but then the others had something to do with it- or considered completely separate form one another.