Comparison between the effects of propofol and midazolam on pentylenetetrazole kindled convulsions in rats

Abstract

Propofol, a short acting intravenous anesthetic which is wildly used for induction and maintenance of anesthesia. In addition, propofol has been successfully used in the management of status epileptics. However, sporadic reports of the occurrence of seizures or seizure like phenomena in epileptic and non‐epileptic patients continue to appear. The purpose of the present study is to examine the effects of intravenous (IV) administration of various doses of propofol and midazolam on pentylentetrazole (PTZ) kindled convulsions in rat.Experiments were conducted in adult females Sprague–Dawley rats (230–250 g). PTZ kindling was induced by intraperitoneal (IP) injection of a subconvulsivant dose of PTZ (35 mg/kg) every alternate day. After each injection of PTZ rats were placed in plexy glass cages and were monitored for 30 minutes for the occurrence of behavioral seizures. Severity of behavioral seizures and seizure score was rated according to Racine scale (Racin, 1972). An animal was considered fully‐kindled when it has had stage 4–5 seizure score on two consecutive trials. To examine the effects of propofol on PTZ kindled convulsions, fully kindled rats (8–10 animals per group) were injected with various doses of propofol (2.5, 5, 10 mg/Kg) prior to PTZ challenge. The drug was administered IV as a single dose through the dorsal tail vein via a 25G butterfly scalp vein cannula. Control animals received an equal volume of saline. Few minutes following drugs or saline injection, rats were challenged with a subconvulsant dose of PTZ (35 mg/Kg) and seizure score for individual animals was recorded. To compare the effects of midazolam on PTZ kindled seizures with these of propofol, the same animal groups were administered various doses of midazolam (2.5, 5, 10 mg/Kg). A period of a two weeks washout was allowed prior to midazolam treatment.The result of our study shows that both anesthetic agents suppressed PTZ kindled seizures in a dose dependent manner indicating that both agents protects against PTZ kindled seizures. However, the effects of midazolam were more profound. Dose response analysis of percent inhibition of kindled seizures shows that the ED50 for midazolam was 1.85 mg/Kg with 95 % CI of (1.71–2.05), whereas the estimated ED50 of propofol was 5.36 mg/kg with 95 % CI of (4.85–5.96).The data of the present study shows that propofol is an effective anticonvulsant against PTZ kindled seizures and provides further support of the anticonvulsant properties reported in different experimental seizures models.Support or Funding InformationThe research was supported by a grant from Arabian Gulf University.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.