Toxicity and enzyme-inducing effect of the antiviral compound mopyridone in mice.
Mopyridone (CAS 82822-14-8, MP) is a new antiviral compound with low acute toxicity in mice. Phenobarbital (PB) induction did not alter MP oral acute toxicity, while methylcholanthrene (MC) and dexamethasone (DEX) induction increased it. MP (1/10 of LD50, 5 days) increased aniline hydroxylase activity (by 158%) and cytochrome P-450 content (by 43%), but has no significant effect on liver N-demethylase activity (ethylmorphine N-demethylase, amidopyrine N-demethylase and benzphetamine N-demethylase) in mouse liver 10,000 x g supernatant. The inducing effect of MP was similar to the effect of MC and differed from the effect of PB. The combination MP + PB exerted an additive inducing effect on aniline hydroxylase (by 390%) and cytochrome P-450 content (by 183%) without affecting PB induced N-demethylases. The character of the MP + PB interaction was similar to that of the MC + PB interaction and suggested different inducing mechanisms of MP and PB. The participation of some cytochrome P-450 isozymes, induced by MC and DEX, in biotransformation of MP to more toxic product(s) was suggested.
Tantcheva
L P
LP
Institute of Physiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Rangelova
D S
DS
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000633:toxicity*; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000633:toxicity*; D066298:In Vitro Techniques; D007928:Lethal Dose 50; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D011744:Pyrimidinones / Q000494:pharmacology* / Q000633:toxicity*
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D011744:Pyrimidinones; C047314:1-morpholinomethyl-tetrahydro-1(1H)-pyrimidinone; D006899:Mixed Function Oxygenases