US EPA

5192214 

Journal Article 

Effect of Chronic Endosulfan Treatment on Pharmacological Actions of Diazepam in Rats 

Paul, V; Kazi, M; Balasubramaniam, E; Sheela, S 

1993 

Yes 

Bulletin of Environmental Contamination and Toxicology
ISSN: 0007-4861
EISSN: 1432-0800 

51 

1 

The effects of endosulfan (115297) on the pharmacologic action of diazepam were studied in rats. Male Wistar-rats were gavaged with 0 or 2mg/kg technical endosulfan daily for 90 days. Twenty four hours after the last dosing they were injected intraperitoneally with 12mg/kg diazepam or 35mg/kg pentobarbitone. The effects of endosulfan on the sedative action of 4mg/kg diazepam were evaluated by measuring changes in spontaneous motor activity. The effects on the muscle relaxation effects of 8mg/kg diazepam were assessed by measuring endurance time in the rota rod test. Endosulfan significantly prolonged latency and shortened the duration of pentobarbitone sleeping time. Sleeping time duration of diazepam was significantly prolonged and its sedative effect was potentiated by endosulfan. Endosulfan alone enhanced spontaneous motor activity. Endosulfan and diazepam interacted synergistically to impair performance on the rota rod test. The authors conclude that endosulfan promotes and potentiates the central depressant actions of diazepam. These effects may reflect enhanced formation of oxazepam, an active diazepam metabolite.