Methotrexate an Old Drug with New Tricks 2019

[pattismith]

https://www.mdpi.com/1422-0067/20/20/5023

This review can be a good point to discuss Methotrexate positive and negative effects on ME/CFS and Fibro, two syndromes that can be comorbid with rheumatic diseases.

In this review, we describe the emerging mechanisms of action of MTX as an anti-inflammatory drug and complementing its well-established immunomodulatory activity. The mechanisms involve adenosine signaling modulation, alteration of cytokine networks, generation of reactive oxygen species and HMGB1 alarmin suppression. We also provide a comprehensive understanding of the mechanisms of MTX toxic effects. Lastly, we discussed the efficacy, as well as the safety, of MTX used in the management of viral-related rheumatic syndromes.

https://www.the-rheumatologist.org/article/old-drugs-can-learn-new-tricks/

methotrexate effect on metabolism can alter brain function by

Upregulation of:

AICAR (This happens 10 hours after MTX intake) promotes awakeness AMPK activator
ADENOSINE (This happens a bit later/48h00 after MTX intake) promotes sleepiness
HOMOCYSTEINE

Downregulation of:

IMP (fatigue cramping exercice intolerance)
INOSINE (fatigue)

What to do to reduce these brain side effects?


-Folinic Acid supplementation 10 to 12 hours after MTX intake
-Caffeine or Theophylline
-Inosine supplementation (and thymidine?)

https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.20516
https://pubmed.ncbi.nlm.nih.gov/16821266/
https://journals.lww.com/ijru/fulltext/2019/14010/use_of_coffee_for_alleviating_methotrexate.20.aspx
https://pubmed.ncbi.nlm.nih.gov/2410122/