Anaesthetic effects of flurazepam alone and in combination with thiopental or hexobarbital evaluated with an EEG-threshold method in male rats.
The anaesthetic effects of a benzodiazepine derivate, flurazepam, and the anaesthetic interaction between flurazepam and 2 barbiturates, thiopental and hexobarbital, were studied in male rats using an EEG-threshold method. The criterion of anaesthesia was defined by a burst suppression in the EEG of 1 sec or more (the "silent second"). The dose needed to induce the criterion was used as the threshold. The data on the interaction were evaluated with the isobolographic method. Flurazepam alone infused with different rates gave an almost V-shaped dose-rate curve. Convulsive activity was seen in all rats in connection with the EEG-criterion. The mortality during anaesthesia increased with increased infusion rates of flurazepam. The anaesthetic interaction between thiopental-flurazepam and hexobarbital-flurazepam was with low admixture of flurazepam, a pronounced potentiation. With increased admixture of flurazepam, an additive interaction with thiopental and flurazepam was obtained, whereas an antagonistic interaction was obtained with hexobarbital and flurazepam. Convulsive activity and mortality during anaesthesia in the interaction studies were only observed in tests where high admixtures of flurazepam were used.
Norberg
L
L
Department of Pharmacology, University of Umeå, Sweden.
Wahlström
G
G
D000777:Anesthetics; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004569:Electroencephalography; D005479:Flurazepam / Q000008:administration & dosage / Q000494:pharmacology*; D006591:Hexobarbital / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013874:Thiopental / Q000008:administration & dosage / Q000494:pharmacology*
D000777:Anesthetics; D006591:Hexobarbital; D005479:Flurazepam; D013874:Thiopental