A Comparison of the Anticonvulsant Effects of Propofol and Thiopentone Against Pentylenetetrazol‐induced Convulsions in the Rat

Hasan, Zuheir; Hasan, Mahmudul; Al-Hader, AbdelFattah; Takrouri, Mohamad Said Maani

doi:10.1111/j.1440-1681.1991.tb01382.x

Cited by 16 publications

(8 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, when administered before PTZ injection, propofol totally prevented PTZ-induced seizure activity in wild-type mice. This is consistent with previous animal studies showing efficacy of propofol in preventing chemically induced seizures, such as pentylenetetrazole (Hasan et al, 1991), strychnine (Al-Muhandis et al, 1991), and lidocaine (Lee et al, 1998). Of interest was the observation that propofol had only a slight effect on PTZ-induced seizures in heterozygote animals.…”

Section: __________________________________________________________ Esupporting

confidence: 90%

Hyperexcitability and epilepsy associated with disruption of the mouse neuronal‐specific K–Cl cotransporter gene

et al. 2002

View full text Add to dashboard Cite

Four genes encode electroneutral, Na+-independent, K-Cl cotransporters. KCC2, is exclusively expressed in neurons where it is thought to drive intracellular Cl- to low concentrations and shift the reversal potential for Cl- conductances such as GABA(A) or glycine receptor channels, thus participating in the postnatal development of inhibitory mechanisms in the brain. Indeed, expression of the cotransporter is low at birth and increases postnatally, at a time when the intracellular Cl- concentration in neurons decreases and gamma-aminobutyric acid switches its effect from excitatory to inhibitory. To assert the significance of KCC2 in neuronal function, we disrupted the mouse gene encoding this neuronal-specific K-Cl cotransporter. We demonstrate that animals deficient in KCC2 exhibit frequent generalized seizures and die shortly after birth. We also show upregulation of Fos, the product of the immediate early gene c-fos, and the significant loss of parvalbumin-positive interneurons, both indicative of brain injury. The regions most affected are the hippocampus and temporal and entorhinal cortices. Extracellular field potential measurements in the CA1 hippocampus exhibited hyperexcitability. Application of picrotoxin, a blocker of the GABA(A) receptor, further increased hyperexcitability in homozygous hippocampal sections. Pharmacological treatment of pups showed that diazepam relieved the seizures while phenytoin prevented them between postnatal ages P4-P12. Finally, we demonstrate that adult heterozygote animals show increased susceptibility for epileptic seizure and increased resistance to the anticonvulsant effect of propofol. Taken together, these results indicate that KCC2 plays an important role in controlling CNS excitability during both postnatal development and adult life.

show abstract

Section: __________________________________________________________ Esupporting

confidence: 90%

Hyperexcitability and epilepsy associated with disruption of the mouse neuronal‐specific K–Cl cotransporter gene

et al. 2002

View full text Add to dashboard Cite

show abstract

“…These findings suggest that propofol is an effective anticonvulsmt, which provides protection against chemically induced convulsions in experimental animals. Thus, the data of the present study provide further support for the anticonvulsant activity of propofol and are consistent with previous findings in the mouse, rat, and rabbit (Lowson et al 1990(Lowson et al , 1991Hasan et al 1991Hasan et al , 1992, which demonstrated that propfol has anticonvulsant activity against pentylenetetrmolinduced seizures.…”

Section: Effects Of Propfol and Thiopntone On Ptx Convulsivesupporting

confidence: 93%

“…1988;Yanny and Christmas 1988). In addition, studies in several animal species have demonstrated that propofol provides protection against pentylenetetrazol-induced seizures (Lowson et al 1990(Lowson et al , 1991Hasan et al 1991 ;Al-Hader et al 1992). Similarly, propfol was found to be an effective antisonvulsant against electrically induced convulsions (Lowson et d. 1990;Hasm and Woolley 1994).…”

Section: Introductionmentioning

confidence: 99%

Effects of propofol and thiopentone on picrotoxin convulsive threshold in the rabbit

Hasan

Khatib²,

Abu-Laban³

1995

Can. J. Physiol. Pharmacol.

View full text Add to dashboard Cite

The purpose of the present study was to examine the effect of intravenous administration of propofol and thiopentone on picrotoxin-induced seizures using the picrotoxin convulsive threshold test in the rabbit. Neither propofol nor thiopentone at a dose of 1.25 mg/kg had any significant effect on picrotoxin seizure threshold. However, at higher doses (2.5, 5, 10 mg/kg) both propofol and thiopentone produced a significant and dose-dependent increase in the picrotoxin convulsive threshold. These findings suggest that propofol is an effective anticonvulsant against picrotoxin-induced seizures in the rabbit.

show abstract

“…In addition to its sedative and anesthetic properties, at low (nonanesthetic) doses propofol confers seizure protection. The anticonvulsant activity of propofol has been demonstrated in diverse animal seizure models (Lowson et al, 1990;Hasan et al, 1991;Micklethwaite and Pleuvry, 1993) and in vitro preparations (Rasmussen et al, 1996;Borowicz and Czuczwar, 2003;Ohmori et al, 2004). Propofol is especially active in animal models of status epilepticus (De Riu et al, 1992;Ahuja and Germano, 1998;Lee and Cheun, 1999), and it is commonly used in the treatment of refractory status epilepticus in humans (Prasad et al, 2001;Arif and Hirsch, 2008).…”

Section: Introductionmentioning

confidence: 99%

Seizure Protection by Intrapulmonary Delivery of Propofol Hemisuccinate

Dhir

Żółkowska

Murphy³

et al. 2010

J Pharmacol Exp Ther

View full text Add to dashboard Cite

The lung provides a portal of entry for drug delivery that could be used to administer anticonvulsant substances to prevent or abort seizures. Here, we demonstrate that intrapulmonary propofol hemisuccinate (PHS) rapidly confers seizure protection in various rodent chemoconvulsant models. Propofol is a powerful anticonvulsant substance at subanesthetic doses, but it is a viscous, water-immiscible oil that is not suitable for intrapulmonary administration. We found that PHS can be formulated as an aqueous solution that is well tolerated when instilled into the lung. High-dose intraperitoneally administered PHS induced loss-of-righting reflex in rats and mice. The onset of action of PHS was delayed in comparison with propofol, suggesting that conversion to propofol is required for activity. A lower dose of PHS (40 mg/kg i.p.) did not cause general anesthesia but protected against pentylenetetrazol (PTZ)-induced seizures in rats. Intrapulmonary administration of an aqueous PHS solution via a tracheal cannula at lower doses (5 and 10 mg/kg) conferred equivalent seizure protection without acute motor toxicity. In mice, intraperitoneal PHS (60 -80 mg/kg) was associated with an elevation in PTZ, bicuculline, picrotoxin, and kainic acid seizure thresholds. Intratracheal PHS was markedly more potent, producing seizure threshold elevations at doses of 10 to 15 mg/kg. In the PTZ threshold model in mice, PHS was active at 5 min, maximally active at 10 min, and no longer active at 20 min. Intratracheal PHS also prolonged the onset of 4-aminopyridine-induced convulsions but did not affect the threshold for N-methyl-D-aspartate-induced convulsions. We conclude that intratracheal administration of an aqueous solution of PHS, a putative propofol prodrug, provides potent seizure protection of rapid onset and brief duration. Intrapulmonary PHS may be useful for preventing the spread of seizures or aborting seizure clusters without causing prolonged sedation.

show abstract

A Comparison of the Anticonvulsant Effects of Propofol and Thiopentone Against Pentylenetetrazol‐induced Convulsions in the Rat

Cited by 16 publications

References 14 publications

Hyperexcitability and epilepsy associated with disruption of the mouse neuronal‐specific K–Cl cotransporter gene

Hyperexcitability and epilepsy associated with disruption of the mouse neuronal‐specific K–Cl cotransporter gene

Effects of propofol and thiopentone on picrotoxin convulsive threshold in the rabbit

Seizure Protection by Intrapulmonary Delivery of Propofol Hemisuccinate

Contact Info

Product

Resources

About