Induction of liver microsomal cytochrome P-450 isozymes by 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide.
1. 1-(2-Chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide (RP 52028), an antagonist of peripheral type benzodiazepine binding sites, a potential anticonvulsant, has been shown to have an inducing effect on drug-metabolizing enzymes. 2. RP 52028 was administered orally at 20-800 mg/kg for 1 week, and enzymic activities were determined using a panel of substrates. Western blot analyses were performed using several specific polyclonal and monoclonal antibodies directed against cytochrome P-450 isozymes. 3. RP 52028 appears to be an inducer of cytochrome P-450 II B1 (P-450b) and related enzymic activities; i.e. benzphetamine, ethylmorphine and aminopyrine demethylation.
Totis
M
M
Centre du Médicament, Université de Nancy, France.
Kremers
P
P
Batt
A M
AM
Van Cantfort
J
J
Siest
G
G
Gielen
J
J
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D015153:Blotting, Western; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D015786:Cytochromes b5 / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007120:Immunochemistry; D007527:Isoenzymes / Q000096:biosynthesis; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D007527:Isoenzymes; D007546:Isoquinolines; D019324:beta-Naphthoflavone; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C037850:PK 11195; D010634:Phenobarbital