Propofol Anticonvulsant Activity in Experimental Epileptic Status

Abstract

We have examined the anticonvulsant properties of propofol in high doses in two experimental models of status epilepticus: generalized pentylenetetrazol (PTZ)-induced seizures and partial, cortically applied penicillin G-induced seizures. Propofol was administered either as a single bolus injection or as a bolus injection followed by an infusion for 1 h. When administered as a single bolus injection, propofol 12 mg kg-1 suppressed electrical and clinical seizures in PTZ generalized epileptic status, and an infusion of 50 mg kg-1 h-1 prevented the reappearance of electrical and clinical signs. In focal epileptic status, the single dose stopped paroxysmal activity and the associated clonic jerks for a few seconds. When the bolus dose was followed by an infusion, the firing bursts were replaced by isolated spikes, and contralateral jerks became sporadic and feeble. The greater efficacy of propofol against PTZ convulsions may be a reflection of the opposite action of the two drugs on neural membrane conductance: PTZ induces paroxysmal neural discharge by enhancing membrane conductance while propofol appears to decrease membrane conductance, thus suppressing paroxysmal discharge. There was no close relationship between blood concentration of the anaesthetic and its clinical effects, at least after a short-term infusion, as used in the present experiments. We suggest that propofol may be a potentially useful drug in status epilepticus in patients in whom benzodiazepines, barbiturates and phenytoin have failed.

Inhibition by propofol of [3H]‐batrachotoxinin‐A 20‐α‐benzoate binding to voltage‐dependent sodium channels in rat cortical synaptosomes

“…The similar pharmacological properties of propofol (this study; Frenkel & Urban, 1991) suggest that an analogous mechanism underlies its Na+ channel blocking effects. Selective antagonism of repetitively active neurones may contribute to both the anticonvulsant (De Riu et al, 1992) and general anaesthetic properties of propofol. Inhibition of Na' channels in depolarized neurones would be expected to exert a neuroprotective effect (Urenjak & Obrenovitch, 1996), although results from studies of the neuroprotective properties of propofol have been inconsistent (Kochs et al, 1992;Ridenour et al, 1992;Amorim et al, 1995;Arcadi et al, 1996).…”

Effects of Propofol on Epileptiform Activity and Hippocampal Morphology in Febrile Convulsions and Pilocarpine Induced Seizures

“…In a study conducted on rabbits, propofol has been demonstrated to suppress epileptic discharges and it has clinically been shown to end seizures in seizure behaviors. In the mentioned study, the time to stop seizures by propofol is identified as 6 minutes and it is reported that seizures did not continue in the follow ups [35]. In another study that compares propofol with other benzodiazepines, it is reported that propofol acts fast, however, it causes relapses at a rate of 19-33%, and therefore, recurring doses might be useful regarding treatment [36].…”

The intensive care treatment of convulsive status epilepticus in the UK

“…It is easy to use, fast acting, and postinfusional recovery of consciousness is quick. There have been a number of favourable reports of its use in status epilepticus [40,41], and it has demonstrated some antiepileptic activity in animal seizure models [42]. It has, however, been reported to precipitate seizures [32] and in intra-operative recordings, it has activated epileptiform discharges on the electrocorticogram [33].…”