title: Inhibition of rat hepatic mixed function oxidases by antimalarial drugs: selectivity for cytochromes P-450 and P-448.
abstract: Intraperitoneal administration of chloroquine, primaquine and quinacrine to rats resulted in inhibition of the hepatic microsomal mixed-function oxidases. The N-demethylation of benzphetamine (cytochrome P-450) was inhibited by chloroquine only while the O-deethylation of ethoxyresorufin (cytochrome P-448) was inhibited by primaquine and quinacrine. When incubated with hepatic microsomes from phenobarbital-pretreated rats, chloroquine and primaquine, but not quinacrine, caused a concentration-dependent inhibition of benzphetamine N-demethylase activity. Incubation of hepatic microsomes from beta-naphthoflavone rats with primaquine and quinacrine, but not chloroquine, resulted in a concentration-dependent inhibition of the O-deethylation of ethoxyresorufin. These observations demonstrate that chloroquine and quinacrine are specific inhibitors of cytochromes P-450 and P-448, respectively.
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D003580:Cytochromes / Q000037:antagonists & inhibitors*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors; D011319:Primaquine / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000962:Antimalarials; D065607:Cytochrome P-450 Enzyme Inhibitors; D003580:Cytochromes; D002738:Chloroquine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; C017170:Cyp1a2 protein, rat; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; C019781:benzphetamine N-demethylase; D010089:Oxidoreductases, N-Demethylating; D011796:Quinacrine; D011319:Primaquine