Posted by Larry Hoover on November 28, 2004, at 17:49:56
In reply to Re: neurotransmitter chart » Larry Hoover, posted by pablo1 on November 28, 2004, at 16:44:02
> Can someone explain the results of this. I searched any flavor of dopamine in humans using dopamine% as a wildcard and got almost 2,000 results.
Funny, I got 3212. ;-)
> I crunched that into excel to sort and there are usually several records for each med, some with very different results.
Make sure you're looking at human receptors, whenever possible.
> I assume the Ki (nM) column is the important one, indicating the effect the drug has on dopamine.
Ki is the equiblibrium inhibitor dissociation constant, which has units of nanomolar (nM). You don't need to know more than that nanomolar is very very dilute.
The tendency of any substance to occupy the binding site of a receptor or an enzyme is measured by its tendency to leave the active site, all on its own. The Ki is the concentration of that substance that is required for the receptor to be 50% occupied (at equilibrium, as many binding events are beginning as those that are ending), in the absence of the natural ligand (e.g. dopamine, for the dopamine receptor). The smaller that value for Ki, the higher its affinity must be, as 50% occupancy occurs at lower substrate concentrations.
> I have no idea what Ki (nM) means, is that agonism or reuptake inhibition.
You only know affinity from the Ki. What the drug will do once bound is another matter altogether. A full agonist will give 100% (or even more) of the effect of the natural ligand, if the drug binds there. An antagonist will give zero effect, even when fully bound. (That has the effect of reducing the receptor population, taking some out of commission temporarily.) A partial agonist will give something between 0 and 100% of the normal agonist response. Then there are inverse agonists, which give an opposite response to that expected from binding to that receptor. You can't tell any of this just from the Ki value. All you know is whether or not the drug has a likelihood of sticking onto that receptor.
> In the recptor column they have either the specific D1, D2, etc or 'Dopamine Transporter' or even some odd ones like 'Dopamine2-like'.
I don't know what dopamine-2-like means, (could be a gene variant not yet fully defined), but the transporter is the reuptake pump. So, transporter binding by an antagonist will inhibit reuptake, for example.
> Does the transporter comment imply reuptake inhibition?
Yes. Generally, anything binding to a reuptake pump will slow down its natural activity, as that's all they do.
> some familiar meds results:
> DOPAMINE D3 Amisulpride 2
> DOPAMINE D2 Amisulpride 1The low value indicates very high affinity at those receptor subtypes. If you click on the hotlink reference to the right, you'll be taken to a Pubmed article that shows that the effect is antagonistic. In other words, amisulpride binds very actively at these two receptors, but inhibits them.
> (but I checked not human tests & got huge numbers)
> Dopamine Transporter Amphetamine,(+) 25
> (not very high?)
> Dopamine Transporter d-AMPHETAMINE 21,000
> DOPAMINE D1 d-AMPHETAMINE 10,000
> DOPAMINE D2 d-AMPHETAMINE 10,000
> DOPAMINE D3 d-AMPHETAMINE 10,000
> Dopamine Transporter d-AMPHETAMINE 190
> Dopamine Transporter d-AMPHETAMINE 116These results for amphetamine tell you that the effect is not greatly due to dopamine receptor binding, but is instead due to reuptake inhibition.
Etc.
Lar
poster:Larry Hoover
thread:420713
URL: http://www.dr-bob.org/babble/20041128/msgs/421498.html