How can a partial dopamine agonist block dopamine pathway

[nomadreid]

I am looking into Aripiprazole. I am not a medical professional.
I am confused by the descriptions of it in Wikipedia:
(a) It is a partial dopamine agonist; i.e., it acts like dopamine to stimulate nerve cells, and
(b) It is an atypical antipsychotic, i.e., it blocks dopamine (and serotonin) pathways
Together, it sounds as if one is robbing Peter to pay Paul: it blocks dopamine in order to itself act as dopamine? This does not sound right. Please clarify. Thanks.

 

[Posty McPostface]

Here's an entry on Wikipedia.

This might be of use also.

 

[nomadreid]

Thanks, Posty McPostface. If my layman's understanding of these articles (where the second one corrects the reference [2] in the first one) is correct (which is unlikely), the combination of effects serves to regulate the dopamine activity by increasing the dopamine effects when there is not enough naturally occurring dopamine is produced and blocking some receptors when there is too much dopamine produced. Is this more or less the correct interpretation?

 

[Posty McPostface]

Well, here's my non-qualified understanding of how Abilify works.

The drug binds to D2-Long receptors blocking excessive activity in an absolute manner while modulating the D2-Short (autoreceptor) activity in either positive or negative manner depending on how much dopamine is available in the synaptic cleft. So, D2-long receptors are sort of blocked to a certain threshold of activity, which the partial agonistic activity of the drug modulates the autoreceptor either positively or negatively. So, in other words, when there isn't enough dopamine in the synaptic cleft, the compound will activate the D2-Short autoreceptor in a manner that causes the D2-Long receptors to heighten their responsiveness to dopamine itself.

Sorry if this is a bad explanation and I hope others can point out any confusion about it. What's worse is that the difference between D2L and D2S isn't all that clear and much information on said differences are lacking on the internet or my Google-fu abilities are lacking.

 

[nomadreid]

Thanks again, Posty McPostface. Your explanation does indeed deepen my understanding. Much better than the other sources I have found on the topic.

 

[Posty McPostface]

On top of what has been said, you might want to read on intrinsic activity of various compounds. Pretty important stuff if you want to have a feeling for what a compound is doing to what receptor and with what magnitude.

 

[Pythagorean]

Partial agonists only somewhat activate receptors, they're not as potent as "full" agonists. So if you put some partial agonist in a place where there's already a full agonist, then they will compete for receptor spots and not allow the full agonist to fully activate receptors, thus its blocking action on the receptors, providing less activation, lowering over all activation.

However, if the partial agonist is in a region where there is not agonist, the partial agonist will be the only thing activating the receptors, so they'll raise activation overall, albeit not as high as an agonist.

I've reached semantic saturation with the word agonist.

 

[nomadreid]

Thanks for the suggestion, Posty McPostface. I shall add this to my attempts at understanding. By "intrinsic activity", I would guess you mean the chemical properties of said compounds?
Thanks for the explanation, Pythagorean. That also adds to my grasp of the over-all regulatory function, if I understand correctly.