Effect of ketamine enantiomers on sound-induced convulsions in epilepsy prone rats

Epilepsy prone rats (Jobe et al, 1982) which had previously been determined to experience relatively mild seizures in response to a sound stimulus were used in this study in order to provide a model which would reveal either proconvulsant or anticonvulsant drug activity. Animals were administered dextrorotatory (+), levorotatory (-), or racemic (+/-) ketamine hydrochloride by intravenous (tail vein) injection and subsequently challenged with a 120 db broad spectrum sound stimulus. Evaluation of drug effect was based on presence/absence of seizure, seizure severity, and convulsive latency (time from onset of stimulus to onset of convulsive episode). Potencies relative to protection against seizure susceptibility were: (+) greater than (+/-) greater than (-), with the ratio of activity of the (+) and (-) isomers comparing to the ratio of activity found by other investigators relative to other effects produced by the isomers. Of all animals which were not fully protected, there were no instances of decrement of seizure severity. At low doses, there was a slight decrease in convulsive latency, which was the only indication of a proconvulsant effect. This effect is probably prevented at the higher doses by the anticonvulsant tendency of the drug.