Effects of Trimethadione, Diphenylhydantoin and Chlordiazepoxide on After-Discharges in Brain of Cat

Abstract

Hunter and Jasper(5) found that stimulation of intralaminar nuclei in the thalamus of the cat produced behavioral arrest, accompanied by a 3 per second spike and slow wave pattern in the EEG. Both behavioral and electrographic effects resembled those seen in petit ma1 epilepsy in man.Trimethadione is clinically effective in petit ma1 epilepsy ( 13). If this type of seizure originates in the intralaminar nuclei, trimethadione should depress this part of the brain. We have tested the effects of trimethadione on the intralaminar central lateral nucleus of the cat, as well as on the adjacent medial dorsal nucleus, cortex and hippocampus. The effects of trimethadione were compared with those of diphenylhydan toin and chlordiazepoxide (Libriuma) .Methods. Forty-one cats were prepared under ether anesthesia. The trachea was cannulated for artificial respiration and the left femoral vein for drug injection. Bipolar concentric electrodes were inserted with the aid of a stereotaxic instrument in central lateral or medial dorsal nuclei of thalamus, on frontal and parietal cortex (ectosylvian gyrus) , and in anterior and posterior hippocampus. All wound edges were infiltrated with procaine. The ether was withdrawn and the cat immobilized with decamethonium (C,,,) .Stimulation was with a Grass S-4 Stimulator. Parameters for medial dorsal nucleus, cortex and hippocampus were pulse duration 2 msec, frequency 40 per sec, duration of stimulation 5 sec, interval between stimulations 5 min. Initial intensity was 1 volt; this was increased by increments of 1 or 2 volts until an after-discharge appeared in the EEG, recorded on a Grass 111-C electroencephalograph. Current was monitored with a Tektronix 502 oscilloscope. Current a t threshold voltage was recorded as "threshold curat Harvard Libraries on June 29, 2015 ebm.sagepub.com Downloaded from

General Pharmacology and Neuropharmacology of Benzodiazepine Derivatives

“…Higher doses of chlordiazepoxide (40 mg' kg-1 i.v.) also decreased the amplitude of the responses in cortex and hippocampus (SCHALLEK and KUEHN, 1963). The findings with chlordiazepoxide were confirmed and extended to other benzodiazepines in a study on unanesthetized, immobilized, and freely moving cats with chronically implanted electrodes (SCHALLEK et aI., 1964).…”

STUDIES ON Β-Pyridylcarbinol AS a PRECURSOR OF NICOTINAMIDE ADENINE DINUCLEOTIDE

“…It has been tentatively concluded that the thalamus is probably the site of action of trimethadione from the implication of the thalamo-cortical system in genesis of petit mal epilepsy (13). This conception was supported by Schallek and Kuehn (12) reporting that the drug is most effecti,,e in raising the threshold for afterdischarge induced by stimulation of the nucleus centralis lateralis of the thalamus. Our results herein confirmed such action of the drug, at a smaller dose of 40 mg/ kg in cats.…”

Benzodiazepines in the Treatment of Epilepsy A Review

“…Diazepam and chlordiazepoxide have been shown to be effective in suppressing the 3 c/sec spike-wave discharges produced by electrical stimulation of the intralaminar region of the thalamus (Guerrero-Figueroa et al 1967 ;Schallek and Kuehn 1963) and in suppressing the paroxysmal discharges produced by epileptogenic lesions in the thalamus (Guerrero-Figueroa et al 1969b;Roldan et al 1971).…”