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Anticonvulsive Effects and Pharmacokinetic Profile of Cannabidiol (CBD) in the Pentylenetetrazol (PTZ) or N-Methyl-D-Aspartate (NMDA) Models of Seizures in Infantile Rats
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SYSNO ASEP 0555874 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Anticonvulsive Effects and Pharmacokinetic Profile of Cannabidiol (CBD) in the Pentylenetetrazol (PTZ) or N-Methyl-D-Aspartate (NMDA) Models of Seizures in Infantile Rats Author(s) Uttl, Libor (FGU-C) ORCID
Hložek, T. (CZ)
Mareš, Pavel (FGU-C) RID, ORCID
Páleníček, T. (CZ)
Kubová, Hana (FGU-C) RID, ORCIDArticle number 94 Source Title International Journal of Molecular Sciences. - : MDPI
Roč. 23, č. 1 (2022)Number of pages 13 s. Language eng - English Country CH - Switzerland Keywords cannabidiol ; epilepsy ; seizures ; NMDA ; pentylentetrazole ; PTZ ; immature rats OECD category Pharmacology and pharmacy R&D Projects EF16_025/0007444 GA MZd - Ministry of Health (MZ) Method of publishing Open access Institutional support FGU-C - RVO:67985823 UT WOS 000741693700001 EID SCOPUS 85121459656 DOI 10.3390/ijms23010094 Annotation In spite of use of cannabidiol (CBD), a non-psychoactive cannabinoid, in pediatric patients with epilepsy, preclinical studies on its effects in immature animals are very limited. In the present study we investigated anti-seizure activity of CBD (10 and 60 mg/kg administered intraperitoneally) in two models of chemically induced seizures in infantile (12-days old) rats. Seizures were induced either with pentylenetetrazol (PTZ) or N-methyl-D-aspartate (NMDA). In parallel, brain and plasma levels of CBD and possible motor adverse effects were assessed in the righting reflex and the bar holding tests. CBD was ineffective against NMDA-induced seizures, but in a dose 60 mg/kg abolished the tonic phase of PTZ-induced generalized seizures. Plasma and brain levels of CBD were determined up to 24 h after administration. Peak CBD levels in the brain (996 +/- 128 and 5689 +/- 150 ng/g after the 10- and 60-mg/kg doses, respectively) were reached 1-2 h after administration and were still detectable 24 h later (120 +/- 12 and 904 +/- 63 ng/g, respectively). None of the doses negatively affected motor performance within 1 h after administration, but CBD in both doses blocked improvement in the bar holding test with repeated exposure to this task. Taken together, anti-seizure activity of CBD in infantile animals is dose and model dependent, and at therapeutic doses CBD does not cause motor impairment. The potential risk of CBD for motor learning seen in repeated motor tests has to be further examined. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2023 Electronic address https://www.mdpi.com/1422-0067/23/1/94
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