Three thiamine analogues differently alter thiamine transport and metabolism in nervous tissue: an in vivo kinetic study using rats.
Thiamine (T) analogues pyrithiamine, oxythiamine or amprolium in amounts 10-1000 times higher than labelled T, were i.p. injected into rats together with 14C-T (30 microg; 46.25 KBq). The radioactivity associated with T and its phosphoesters in the plasma and cerebral cortex, brainstem, cerebellum, and sciatic nerve were determined at time intervals from 0.25 to 240 h from injection. The experimental data obtained were processed with a mathematical compartmental model that calculated the fractional rate constants. These are the amount of content in a given compartment that is replaced in 1 h and expressed in per hour. The results showed that all three analogues inhibited thiamine entry from plasma. Instead, oxythiamine enhanced T phosphorylation to T pyrophosphate (TPP); amprolium and oxythiamine enhanced TPP dephosphorylation to monophosphate (TMP); pyrithiamine reduced TPP dephosphorylation and TMP formation, while none of the analogues modified TMP dephosphorylation to T. In conclusion, in living rats, the action of T analogues was much more complex than could be expected from their structure and action in vitro.
Rindi
G
G
Department of Experimental Medicine, Section of Human Physiology, University of Pavia, Pavia, Italy.
Patrini
C
C
Nauti
A
A
Bellazzi
R
R
Magni
P
P
D000670:Amprolium / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001835:Body Weight; D002250:Carbon Radioisotopes; D007700:Kinetics; D008297:Male; D009417:Nerve Tissue / Q000378:metabolism*; D010119:Oxythiamine / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011745:Pyrithiamine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013831:Thiamine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D013833:Thiamine Monophosphate / Q000378:metabolism; D013835:Thiamine Pyrophosphate / Q000378:metabolism; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D010119:Oxythiamine; D013833:Thiamine Monophosphate; D011745:Pyrithiamine; D000670:Amprolium; D013835:Thiamine Pyrophosphate; D013831:Thiamine