Research ReportAnticonvulsant properties of an oral ketone ester in a pentylenetetrazole-model of seizure

- A synthetic ketone ester has anti-seizure efficacy.
- Ketogenic diet in-a-pill sounds possible.
- Blood ketone bodies are confirmed to have an acute anti-seizure efficacy.

The ketogenic diet is known to have an anti-epileptic effect; in fact it is currently used to treat drug resistant epilepsies. The efficacy of this diet is thought to be correlated to the elevation of blood ketone bodies. Because of problems with compliance to this diet, there is an interest in evaluating alternative pharmacological treatments that can have anti-seizure effects by elevating ketone bodies. In the present experiment, an orally administered synthetic ketone ester (R,S - 1,3-butanediol acetoacetate diester, or BD-AcAc2) was evaluated for its anti-seizure efficacy in a rat model. The threshold for seizure induction with progressive intravenous infusion of pentylenetrazole (PTZ) was evaluated in anesthetized Wistar rats two hours after a single 1 ml intragastric administration of BD-AcAc2 (i.e. 4 g/kg b.w., treated group) or water (control group). After correction for the dose of anesthetic, the results showed that the administration of BD-AcAc2 induced an elevation of the PTZ threshold (140±11 mg/kg for the treated group, 122±6 mg/kg for the control group), along with an increased level of blood β-hydroxybutyrate (2.7±0.3 mM for the treated group, 1.4±0.1 mM for the control group). This result suggests that ketone esters may pave the road towards the establishment of a “ketogenic diet in a pill”.