title: The effect of chronic felbamate administration on anticonvulsant activity and hepatic drug-metabolizing enzymes in mice and rats.
abstract: The possibility of tolerance development from chronic administration of felbamate (FBM) was investigated in mice and rats. Chronic administration (15 days) of FBM (150 mg/kg i.p.) in mice had no significant effect on either intravenous pentylenetetrazol (PTZ) seizure threshold or hexobarbital sleep time; however, hexobarbital sleep time was significantly increased after a single dose. Chronic administration (5-7 days) of FBM (48 or 95 mg/kg orally) in rats also had no significant effect on either maximal electroshock seizure activity or hexobarbital sleep time. Chronic administration of FBM at 238 mg/kg slightly decreased anti-subcutaneous PTZ activity in chronically treated rats (one of eight protected) as compared with those receiving only a single dose (three of eight protected), but there was no significant change in hexobarbital sleep time. Chronic treatment of rats for 7 days with 48 mg/kg had no significant effect on any hepatic parameters. However, 95 or 238 mg/kg of FBM significantly increased p-nitroanisole O-demethylase activity. It is concluded that the increased hexobarbital sleep time induced by an acute dose of FBM reflects the CNS-depressant effect of the substance. The increased p-nitroanisole O-demethylase activity observed after chronic administration may be indicative of some liver microsomal induction. Overall, FBM in doses ranging from 48 to 238 mg/kg appears to have minimal potential for tolerance development.
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004597:Electroshock; D004827:Epilepsy / Q000378:metabolism*; D000078328:Felbamate; D006591:Hexobarbital / Q000494:pharmacology; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010090:Oxidoreductases, O-Demethylating / Q000378:metabolism; D010433:Pentylenetetrazole; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012890:Sleep / Q000187:drug effects
chemical_list: D000927:Anticonvulsants; D048448:Phenylcarbamates; D011409:Propylene Glycols; D011506:Proteins; D003577:Cytochrome P-450 Enzyme System; D006591:Hexobarbital; C026048:4-nitroanisole O-demethylase; D010090:Oxidoreductases, O-Demethylating; D009251:NADPH-Ferrihemoprotein Reductase; D010433:Pentylenetetrazole; D000078328:Felbamate