Effect of anti-relapse antimalarial compound CDRI 80/53 and primaquine on hepatic mixed function oxidase system of rhesus monkey.
A potential anti-relapse antimalarial compound CDRI 80/53 [N1-(3-acetyl-4-5-dihydro-2-furanyl)-N4-(6-methoxy-8-quinolinyl)1,4- pentanediamine] at 7.5 mg/kg body weight and primaquine at 6.0 mg/kg body weight did not cause any significant change in the status of hepatic microsomal mixed function oxidase system of rhesus monkeys, when given orally for 7 days. Further, the extension of the treatment at the same dossier up to 21 days resulted in impairment of the different indices of the MFO system. The compound CDRI 80/53 inhibited cytochrome P-450, aminopyrine-N-demethylase, aniline and benzo(a)pyrene hydroxylases, cytochrome b5 and haem levels by 17, 11, 58, 0, 36 and 35% whereas the inhibition caused by primaquine was 34, 40, 72, 54, 39 and 38% respectively, establishing that the cytochrome P-450 dependent mono-oxygenase system of monkey liver was comparatively less suppressed by compound CDRI 80/53. The cessation of the compound/drug treatment resulted in almost complete reversal of all the MFO activities to normal in a period of about 6 weeks.
Pandey
V C
VC
Division of Biochemistry, Central Drug Research Institute, Lucknow, India.
Puri
S K
SK
Sahni
S K
SK
Srivastava
P
P
Dutta
G P
GP
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015786:Cytochromes b5 / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008253:Macaca mulatta; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D011319:Primaquine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000634:Aminoquinolines; D000962:Antimalarials; D006418:Heme; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D011319:Primaquine; C063469:bulaquine