Impaired mutagenic activities of MPDP(+) (1-methyl-4-phenyl-2,3-dihydropyridinium) and MPP(+) (1-methyl-4-phenylpyridinium) due to their interactions with methylxanthines.
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a neurotoxin causing symptoms that resemble those observed in patients suffering from Parkinson's disease. However, in animal or human organisms, MPTP is converted to MPDP(+) (1-methyl-4-phenyl-2,3-dihydropyridinium) and further to MPP(+) (1-methyl-4-phenylpyridinium); the latter compound is the actual neurotoxin. In this report, we demonstrate that MPDP(+) and MPP(+) can form stacking complexes with methylxanthines (caffeine and penthoxifylline), which leads to significant impairment of the biological activity of these toxins (as measured by their mutagenicity).
Ulanowska
Katarzyna
K
Department of Molecular Biology, University of Gdańsk, Kładki 24, Gdańsk, Poland.
Piosik
Jacek
J
Gwizdek-Wiśniewska
Anna
A
Wegrzyn
Grzegorz
G
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology*; D002151:Calorimetry; D004347:Drug Interactions; D008958:Models, Molecular; D015394:Molecular Structure; D009153:Mutagens / Q000494:pharmacology; D010431:Pentoxifylline / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D013054:Spectrophotometry, Atomic; D014733:Vibrio / Q000187:drug effects / Q000235:genetics
D009153:Mutagens; D011726:Pyridinium Compounds; D002110:Caffeine; C044755:1-methyl-4-phenyl-2,3-dihydropyridinium; D015655:1-Methyl-4-phenylpyridinium; D010431:Pentoxifylline