(https://www.medikamente-per-klick.de/im ... 3_de_o.pdf).
Zum Schema: 5-FU besteht aus einem monofluorierten Pyrimidinring, dessen Abbau via Hydridtransfer stattfindet. Die hydrolytische Ringspaltung zwischen Position 3 und 4 leitet eine Konversion des Hauptmetaboliten Fluor-Beta-Alanin (FBAL) zu Fluoracetat oder 2-Fluor-3-hydroxypropansäure (FHPA) ein (welche ebenfalls zu Fluoracetat konvertiert werden kann). Offenbar setzt FBAL auch anorganisches Fluorid frei:
- unnamed (1).png (92.82 KiB) 4063 mal betrachtet
- unnamed (1).png (92.82 KiB) 4063 mal betrachtet
Studien:
Biochemical Basis for Fluorouracil Neurotoxicity: The Role of Krebs Cycle Inhibition by Fluoroacetate.
http://jamanetwork.com/journals/jamaneu ... act/569964
The acute cerebellar syndrome in 5-fluorouracil chemotherapy: a manifestation of fluoroacetate intoxication.
https://www.ncbi.nlm.nih.gov/pubmed/5535078
Metabolites of 5-fluorouracil, alpha-fluoro-beta-alanine and fluoroacetic acid, directly injure myelinated fibers in tissue culture.
https://www.ncbi.nlm.nih.gov/pubmed/8811119
5-Ethynyluracil (GW776): effects on the formation of the toxic catabolites of 5-fluorouracil, fluoroacetate and fluorohydroxypropionic acid in the isolated perfused rat liver model.
https://www.ncbi.nlm.nih.gov/pmc/articl ... 3-0060.pdf
The anti-cancer drug 5-fluorouracil is metabolized by the isolated perfused rat liver and in rats into highly toxic fluoroacetate.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151255/
Neurotoxic effects of alpha-fluoro-beta-alanine (FBAL) and fluoroacetic acid (FA) on dogs.
https://www.ncbi.nlm.nih.gov/pubmed/15206584