Effect of long-term multiple nifedipine administration on the antinociceptive activity of acetaminophen.
The influence of long-term nifedipine administration on the antinociceptive activity of acetaminophen on hexobarbital sleeping time and liver monooxygenase and synthetase activities was studied in male albino mice. Nifedipine was administered orally at a dose of 25 mg/kg daily for 14 and 21 days. The nociceptive response was determined by the acetic acid writhing test. There was no significant difference in the antinociceptive effect of acetaminophen after treatment with nifedipine for 14 days. Nifedipine caused enzyme induction, which was demonstrated by shortened hexobarbital sleeping time, enhanced ethylmorphine-N-demethylase (EMND), aniline-4-hydroxylase (AH), ethoxycoumarine-O-deethylase (ECOD), UDP-glucuronyl transferase (UDPGT), glutathione-S-transferase (GST) and NADPH-cytochrome c reductase activity and increased content of cytochrome P450 and cytochrome b5. It is assumed that this effect of nifedipine on acetaminophen analgesia is associated with the changes (acceleration) in acetaminophen metabolism in the liver after repeated administration of the drug.
Koleva
M
M
Laboratory of Drug Toxicology, Institute of Physiology, Bulgarian Academy of Sciences, Sofia, Bulgaria. mrkoleva@iph.bio.bas.bg
Dimova
S
S
D000082:Acetaminophen / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015786:Cytochromes b5 / Q000378:metabolism; D004347:Drug Interactions; D006591:Hexobarbital; D006993:Hypnotics and Sedatives; D008297:Male; D051379:Mice; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism
D018712:Analgesics, Non-Narcotic; D002121:Calcium Channel Blockers; D006993:Hypnotics and Sedatives; D000082:Acetaminophen; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D006591:Hexobarbital; D009543:Nifedipine