Effect of Bumetanide Administration on the Pharmacoresistant Seizure to Lamotrigine in Electrical Amygdala Kindled Rats Publisher



Kheiri R¹ ; Kebriaeezadeh A^{1, 2} ; Mirnajafizadeh J³ ; Sayyah M⁴ ; Sharifzadeh M¹ ; Khodadadi M³ Show Affiliations
Source: Pharmaceutical Chemistry Journal Published:2023

Abstract

In recent decades, 30 – 40 percent of epilepsy patients did not get relief from seizures by antiepileptic medications. In the present study, the effect of bumetanide (as NKCC isoform blocker) on pharmacoresistant seizure was investigated on three laboratory models of seizure were used in this study. In 6-Hz electroshock model, mice were stimulated via corneal electrodes connected by 44 mAconstant current intensity at a frequency of 6 Hz for 3 second following drug administration, and then, the seizure severity was observed for at least 10 sec. In the second model, lamotrigine-sensitive seizures were induced by amygdala kindling. The last model was lamotrigine-resistant, in which rats were administrated 5 mg/kg/day lamotrigine (i.p.) at 60 min before kindling stimulation until the animals became kindled. Results showed that the administration of bumetanide alone (10 mg/kg) or co-administration of bumetanide with lamotrigine (5 and 10 mg/kg respectively) did not have significant influence on kindling parameters in 6 Hz model and lamotrigine-resistant rats. It was concluded that bumetanide had anticonvulsant effect in lamotrigine-sensitive rats but did not show the ability to overcome drug-resistant seizure, although it could be a powerful medication, either in combination with anti-seizure regimens or even alone, in reducing the drug-sensitive seizure conditions. © 2023, Springer Science+Business Media, LLC, part of Springer Nature.