So recently I have come across these two completely contradictory methods for treating cancer, one solely relying on application of D2R agonists (such as quinpirole) for treatment of lung cancer and the other one (that is recently published) claims the application of D2R antagonists (such as aspimozide and haloperidol) for treatment of pancreatic cancer. It is quite confusing to me how can two totally paradoxic methods have the same effect on the cancerous cells. Can someone guide me on which method is actually useful.
http://www.sciencedirect.com/science/article/pii/S1574789114002038
http://www.sciencedirect.com/science/article/pii/S0016508516349824
This is the way I understand it.
The same chemical that excites a receptor at a low dosage may be considered to block it at a high dosage, potentially. This only works out if the chemical/drug in question has a dopaminergic effect, but less than that produced by the docking of the 'real' dopamine.
If the individual has LOW dopamine, our chemical that fits into the (previously empty) receptor excites it and produces a dopaminergic effect.
If our individual has HIGH dopamine receptor activity, then our chemical can snug into the receptor and prevent dopamine from docking. This decreases the dopaminergic effect, since this chemical has a weaker dopamine-releasing effect than dopamine would have.
Thus a chemical can have opposite effects depending on its dosage.
A second mechanism that may occur is where high doses may desensitize the receptor, leading to an inhibition effect over time. Here's a paper that discusses this in the context of dopamine: Article Opposite effects of low versus high dose haloperidol treatme...
Hope this was helpful!
appreciate it, this was totally enlightening and makes a lot of sense. Thanks again
I have found moclobemide at very low dose (75-150mgm daily in the morning up to early afternoon if dose is divided) to be a very effective medication in the treatment of some neurological features of ME/CFS (myalgic encephalmyelitis / chronic fatigue syndrome) It has an effect which I understood to be due to its dopaminergic action. The patients response is a clear head, concentrate better, as improved coping skills. Much higher doses had no effect or were not tolerated.
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