Yeah, I thought it was just the brand name, Azilect, that's expensive but the generic came out a number of years ago and it's still like $400. Perhaps it does have a high cost of manufacturing, but it could also just be the generic manufacturers want to have a high profit margin. There's no incentive for them to make less money, especially since there's so few of them making it.
Rasagiline feels a bit cleaner than Selegiline, less stimulating I guess. However, at the same time it feels less motivating/energizing. Part of the reason might be due to the metabolites produced by selegiline, but even sublingual selegiline at 1.25 mg is quite stimulating. Selegiline itself has catecholamine activity enhancing properties, though I don't know if it's clinically significant.
Also, Selegiline increases the number of dopamine transporters even after a single dose whereas Rasagiline does not.
Striatal levels of DAT were elevated after 1 and 21 days treatment with selegiline, but were not affected by clorgyline, rasagiline, nomifensine or amphetamine.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571229/
It appears that Selegiline may have additional effects independent from its MAO-B inhibition. From the same article:
One possibility is that (−)-amphetamine and (−)-methamphetamine produced in vivo from selegiline alter the expression of DAT, since in addition to the classical effects of amphetamine on the neuronal cell, it has been shown that amphetamine can induce up-regulation of zif/268 mRNA expression in rat forebrain (Wang & McGinty, 1995). However amphetamine given in the same dose as selegiline did not affect DAT level in our study. Selegiline has been shown to alter the expression of mRNA for a variety of proteins such as tyrosine hydroxylase, L-aromatic amino acid decarboxylase and glial fibrillary acidic protein (Li et al., 1992; 1993; Vrana et al., 1992) in lower dosage than is needed to influence dopamine metabolism.
In conclusion, we found functional evidence for a reduction in striatal dopamine uptake in vivo by selegiline, together with increased synthesis of dopamine transporter molecules. The increase in expression of transporter molecules may be a property of selegiline separate from its effect on MAO. From the present results we cannot tell whether the increase in the transporter expression is due to increase in transporter synthesis or reduction in its metabolism.
As for methylfolate, I find it helpful in reducing agitation and eye fatigue. I often have trouble maintaining focus on even a single word and feel restlessness in my eyes. Methylfolate directly decreases it and I've found nothing else that can do this. It can also improve my mood and sustained attention as well as some aspects of cognition, but it often does the opposite which is why I barely took it in 2022.
It needs to be balanced with B12 to work properly but I've never been able to figure out the dosing for myself. For instance, if I take methylfolate 1000 mcg every 3 days for a week then it will start having negative effects by the 3rd dose. Taking B12 either in the form of methylcobalamin or adenosylcobalamin would alleviate the negative effects and for a day I'd have some positive effects.
However, these positive effects only last for that one day and taking either more methylfolate or b12 the next day just causes negative effects.
