What drugs do you have in mind?
For dopamine, Levodopa and Sapropterine can be used.
For the excessive Tryptophan and IDO upregulation, there are two options. First, there are immuno-suppressive vaccinations (e.g. CTB) but they aren't FDA-approved as far as I know (
10.3390/vaccines3030703).
Second, there is norepinephrine and IVIG, both of which are approved by the FDA (
10.1371/journal.pone.0045491).
But we can think this one step further.
These effects occurred mainly via the β(2)-adrenergic receptor.
Against this receptor type, as we know, often exist antibodies in CFS/ME patients. There is a huge range of
β(2)-adrenergic agonists available for this if someone prescribes them to you. The problem with these medications are always the side effects, e.g. Tachycardia, Tremors, Excessive Sweating, Anxiety, Insomnia, Agitation. These are common symptoms in CFS/ME already. You wouldn't want to exacerbate them.
I took low doses of norepinephrine occasionally for some time since I also had allergies with breathing issues. The half dose was sufficient for an effect like others might experience when taking meth, which basically is a large dose of the same medication dissolved from the antihistamine and then sold as a drug. The effect was so severe, I couldn't sleep, my heart was racing, strong heartbeats, hyperactive, euphoria, intense thirst. And the wear-off was the same as well, which means I was completely ruined afterward. Very small doses might be more helpful, but it's impossible to get prescribed separately due to the meth issue. They even took the combo with the third-generation antihistamine off the market here.
The problem is that norepinephrine affects the whole body, while the IDO trap only affects certain cells. You'd need a delivery system to these cells. These technologies exist in cancer research.
Another option that is being
discussed is Naltrexone, which can enhance the dopaminergic and norepinephrinergic systems indirectly, which should avoid severe side effects as known from the previous drug candidates (
10.1016/0006-8993(85)90794-2).
Regarding NAD+, this is just an indirect effect. The primary problem is the lack of kynurenine availability. Kynurenine has a range of effects parallel to the Niacin pathway, primarily of immunological importance (
10.3389/fimmu.2020.00031). By taking NAD+ injections, for example, the positive effects of kynurenine and Niacin are skipped. Kynurenines are opioid receptor agonists (
10.3390/biom10020284). So one method to increase their saturation might be taking opioid receptor antagonists such as Naltrexone. But this is just theoretical based on my understanding. We would need to know the receptor affinity of all Kynurenine metabolites. Nevertheless, when Naltrexone interacts with this common receptor, it's possible that there are also other mechanisms of actions within the Kynurenine system.
To compensate for the limited Niacin supply, low doses of Niacin can also help. Independent from that, there still is a lack of oxidation, which reduces ATP replenishment, oxidative phosphorylation, and NAD+ balance. The keto diet can compensate for that to a limited extent. A less potent alternative to the keto diet are BHB supplements. Moreover, chromium picolinate could help normalize the potentially low chromium and picolinate levels.
