ArticleCNS neuroscience & therapeutics2022
Pronounced antiseizure activity of the subtype-selective GABA
Article in CNS neuroscience & therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04244175 (A Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicenter Trial of CVL-865 as Adjunctive Therapy in Adults With Drug-Resistant Focal Onset Seizures), which is not on this map. Cited by 9 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicenter Trial of CVL-865 as Adjunctive Therapy in Adults With Drug-Resistant Focal Onset Seizures (REALIZE Trial)
Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Antiseizure Medications in Development: Novel Mechanisms, Precision Therapy, and the Move Towards Disease Modification.Current issues in molecular biology · 2026Review
- Review
- ENX-101, a GABAEpilepsia · 2025Article
- New epilepsy therapies in development.Nature reviews. Drug discovery · 2024Review
- Review
- Established and emerging GABAFrontiers in pharmacology · 2024Review
- Genetic Background of Epilepsy and Antiepileptic Treatments.International journal of molecular sciences · 2023Review
- New GABA-Targeting Therapies for the Treatment of Seizures and Epilepsy: II. Treatments in Clinical Development.CNS drugs · 2023Review
- Pronounced antiseizure activity of the subtype-selective GABACNS neuroscience & therapeutics · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimDarigabat is an α2/3/5 subunit-selective positive allosteric modulator of GABA
methodsThe MTLE model is generated by single unilateral intrahippocampal injection of low dose (1 nmole) kainic acid in adult mice, and subsequent epileptiform activity is recorded following implantation of a bipolar electrode under general anesthesia. After a period of epileptogenesis (~4 weeks), spontaneous and recurrent hippocampal paroxysmal discharges (HPD; focal seizures) are recorded using intracerebral electroencephalography. The number and cumulated duration of HPDs were recorded following administration of vehicle (PO), darigabat (0.3-10 mg kg
resultsDarigabat dose-dependently reduced the expression of HPDs, demonstrating comparable efficacy profile to diazepam at doses of 3 and 10 mg kg
conclusionsDarigabat exhibited a robust efficacy profile in the MTLE model, a preclinical model of drug-resistant focal epilepsy. A Phase II proof-of-concept placebo-controlled, adjunctive-therapy trial (NCT04244175) is ongoing to evaluate efficacy and safety of darigabat in patients with drug-resistant focal seizures.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.