title: Anticonvulsant properties of an oral ketone ester in a pentylenetetrazole-model of seizure.
abstract: 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 ± 0.3mM for the treated group, 1.4 ± 0.1mM for the control group). This result suggests that ketone esters may pave the road towards the establishment of a "ketogenic diet in a pill".
authors.affiliation: Department Medicine and Surgery, University of Salerno, via Allende snc, Baronissi, SA, Italy. Electronic address: aviggiano@unisa.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Viggiano
authors.affiliation: Department of Molecular Pharmacology and Physiology, Hyperbaric Biomedical Research Laboratory, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., MDC 8, Tampa, Florida; External Pharmacy of Fatebenefratelli Hospital, Viale Principe di Napoli 14/A, Benevento, Italy. Electronic address: raf.pilla@gmail.com.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Pilla
authors.affiliation: Savind, Inc., Seymour, IL, United States.
authors.forename: Patrick
authors.initials: P
authors.lastname: Arnold
authors.affiliation: Department of Experimental Medicine, Second University of Naples, Via De Crecchio 8, Italy. Electronic address: marcellino.monda@unina2.it.
authors.forename: Marcellino
authors.initials: M
authors.lastname: Monda
authors.affiliation: Department of Molecular Pharmacology and Physiology, Hyperbaric Biomedical Research Laboratory, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., MDC 8, Tampa, Florida. Electronic address: ddagosti@health.usf.edu.
authors.forename: Dominic
authors.initials: D
authors.lastname: D'Agostino
authors.affiliation: Department Medicine and Surgery, University of Salerno, via Allende snc, Baronissi, SA, Italy; UO Child and Adolescent Neuropsychiatry, Medical School, University of Salerno, Largo Città di Ippocrate snc, Salerno, Italy.
authors.forename: Giangennaro
authors.initials: G
authors.lastname: Coppola
mesh_terms: D000090:Acetoacetates / Q000008:administration & dosage*; D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage*; D002072:Butylene Glycols / Q000008:administration & dosage*; D003292:Convulsants / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D008297:Male; D010433:Pentylenetetrazole / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced* / Q000178:diet therapy*
chemical_list: C094875:1,3-butanediol diacetoacetate; D000090:Acetoacetates; D000927:Anticonvulsants; D002072:Butylene Glycols; D003292:Convulsants; D010433:Pentylenetetrazole
keywords: Ketogenic diet; Ketone ester; Pentylenetetrazole; Seizure threshold