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.
|
Authors | E A Swinyard, J H Woodhead, M R Franklin, R D Sofia, H J Kupferberg |
Journal | Epilepsia
(Epilepsia)
Vol. 28
Issue 3
Pg. 295-300
( 1987)
ISSN: 0013-9580 [Print] United States |
PMID | 3107974
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- Anticonvulsants
- Phenylcarbamates
- Propylene Glycols
- Proteins
- Cytochrome P-450 Enzyme System
- Hexobarbital
- 4-nitroanisole O-demethylase
- Oxidoreductases, O-Demethylating
- NADPH-Ferrihemoprotein Reductase
- Pentylenetetrazole
- Felbamate
|
Topics |
- Animals
- Anticonvulsants
(pharmacology)
- Cytochrome P-450 Enzyme System
(metabolism)
- Electroshock
- Epilepsy
(metabolism)
- Felbamate
- Hexobarbital
(pharmacology)
- Male
- Mice
- Microsomes, Liver
(metabolism)
- NADPH-Ferrihemoprotein Reductase
(metabolism)
- Oxidoreductases, O-Demethylating
(metabolism)
- Pentylenetetrazole
- Phenylcarbamates
- Propylene Glycols
(pharmacology)
- Proteins
(metabolism)
- Rats
- Rats, Inbred Strains
- Sleep
(drug effects)
|