pentylenetetrazole (BTD-001) / Balance Therap - LARVOL DELTA

A fluorescent probe for concurrent detection of cysteine, homocysteine, and superoxide anion. (PubMed, Sci Adv) - "In pentylenetetrazole (PTZ)- and acetaminophen (APAP)-induced models of epilepsy and liver injury, BPC revealed notable alterations in Cys, Hcy, and O2•- levels, providing mechanistic insights into redox dysregulation. Moreover, BPC successfully tracked redox restoration following N-acetylcysteine (NAC) treatment. These findings establish BPC as a versatile tool for redox biology and highlight its promise for diagnostic and therapeutic applications."

Journal • CNS Disorders • Epilepsy • Hepatology • Liver Failure

Boldo leaves reduce seizures, neuroinflammation, and hemichannel activity in a murine model of chronic epilepsy. (PubMed, Biol Res) - "Seizure severity was assessed in a pentylenetetrazole-induced kindling mouse model...Importantly, Boldo was more effective than valproate in reducing plasmatic levels of inflammatory and oxidative stress markers. These findings indicate that Boldo, by inhibiting these HCs, could provide a valuable therapeutic strategy to mitigate neuroinflammation in epilepsy, highlighting the clinical potential of this readily available medicinal herb."

Journal • Preclinical • CNS Disorders • Epilepsy • Inflammation • IL1B • IL6 • TNFA

Temporal Dynamics of c-Fos Expression in a Zebrafish Larva Model of Pentylenetetrazole-Induced Seizures. (PubMed, Zebrafish) - "The observed peak expression at 45 min suggested an optimal window for evaluating c-Fos expression in the PTZ-induced seizures model of zebrafish larva. These findings provided a valuable reference for selecting experimental endpoints in zebrafish larva seizure studies and enhanced the reliability of c-Fos as a marker of neuronal activation."

Journal • CNS Disorders • Epilepsy • FOS

Preventive effects of vitamin D on epileptic seizures and its regulation of PTEN and autophagy in acute epilepsy mouse models. (PubMed, Nutr Neurosci) - "VitD or vehicle was administered 40 min before pentylenetetrazole (PTZ) or kainic acid (KA) given intraperitoneal injection (i.p)...(2) KA-induced epilepsy caused more severe damage with stronger autophagy activation. (3) VitD pretreatment mitigated seizures by modulating CaSR, PTEN, and autophagy, showing greater efficacy in the PTZ model."

Journal • Preclinical • CNS Disorders • Epilepsy • PTEN

Design and Development of Sulfonamide-Chalcones as Antiepileptic Candidates: Computational and Zebrafish-Based Validation Approaches. (PubMed, ACS Omega) - "All compounds showed a favorable safety profile and antiepileptic potential, as validated using a pentylenetetrazole (PTZ)-induced seizure zebrafish model. In conclusion, this integrated computational-experimental approach highlights the therapeutic potential of sulfonamide-chalcone hybrids, particularly 4-(trifluoromethyl)-N-(4-(3-(4-(trifluoromethyl)-phenyl)-acryloyl)-phenyl)-benzenesulfonamide (compound 20), as potential positive allosteric modulators of the GABAA receptor, offering a viable pathway for the development of next-generation AEDs with improved efficacy and safety profiles."

Journal • CNS Disorders • Epilepsy

DNA demethylation modulates GLUT1, neurovascular metabolic targets and seizures in rats with cortical dysplasia post seizure induction (AES 2025) - "Then, induced a seizure with a sub-dose of pentylenetetrazole (second hit)...We evaluated the impact of DNA methylation inhibitor decitabine/5-Aza-2-deoxycytidine on the enzyme DNA methyltransferase 1 (DNMT1) activity... Together, these findings confirm that demethylation strategy modulates GLUT1, and key neurovascular metabolic targets, decreases seizure score and alters mTOR regulatory pathways in CD rats post seizure induction. Therefore, DNA demethylation therapeutic intervention maybe a promising approach in managing seizures and regulating the GLUT1-mTOR signaling pathway affected by cerebral glucose metabolism in epilepsy with cortical dysplasia."

Epigenetic controller • Preclinical • Cardiovascular • CNS Disorders • Epilepsy • DNMT1 • SLC2A1

Visual detection of seizures in mice using supervised machine learning. (PubMed, Cell Rep Methods) - "Using the pentylenetetrazole (PTZ)-induced seizure model in mice, we trained video-only classifiers to predict ictal events and combined these events to predict composite seizure intensity for a recording session, as well as time-localized seizure intensity scores. Our results show that seizure events and overall intensity can be rigorously quantified directly from overhead video of mice in a standard open field using supervised approaches. These results enable high-throughput, non-invasive, and standardized seizure scoring for neurogenetics and therapeutic discovery."

Journal • Preclinical • CNS Disorders • Epilepsy

Effect of ELF-EMF on cognitive functions, analgesia, and oxidative stress in rats with PTZ-induced epilepsy. (PubMed, Electromagn Biol Med) - "This study aimed to examine the impacts of extremely low-frequency (ELF)-electromagnetic field (EMF) on cognitive functions and analgesia in terms of total oxidant status (TOS) and total antioxidant status (TAS) in the experimental pentylenetetrazole (PTZ)-induced epilepsy model...Also, TOS statistically significantly increased in the hippocampus in both PTZ and ELF-EMF+ PTZ groups compared with the sham group (p < 0.001). ELF-EMF decreased the increased TOS in the hippocampus of rats in the PTZ group."

Journal • Preclinical • CNS Disorders • Epilepsy

Modified Pentylenetetrazole Model for Acute Seizure Induction in Rats. (PubMed, Biomedicines) - "The behavioral and ECoG assessments of seizures showed a strong agreement in the latency and duration (r = 0.97, p < 0.0001; r = 0.81, p < 0.05, respectively) with minimal bias in Bland-Altman analysis, confirming that both methods provide statistically comparable and interchangeable measures of seizure characteristics. Our findings highlight the robustness and reproducibility of this modified PTZ-induced acute seizure model, offering an improved preclinical platform for studying seizure pathophysiology and screening for novel therapeutic interventions."

Journal • Preclinical • CNS Disorders • Epilepsy

Cannabidiol potentiates phenobarbital effects in the control of pentylenetetrazole (PTZ)-induced epileptic seizures in neonate rats. (PubMed, Front Pediatr) - "However, CBD (30, 100, or 200 mg/kg) significantly enhanced the efficacy of a subeffective dose of PB (10 mg/kg). These results indicate a dose-dependent potentiation by CBD of PB effects, supporting the potential of CBD as an adjunct therapy for neonatal seizures."

Journal • Preclinical • CNS Disorders • Epilepsy

History of the Racetams. (AES 2025) - "Funding: None Rationale: Levetiracetam (LEV) has been a blockbuster drug and drew attention to a unique mechanism of action. The history of antiseizure medication (ASM) discovery provides lessons for new drug development. We reviewed literature and conducted interviews with the investigators involved. Piracetam was synthesized in 1964 by Giurgea in a project attempting to develop GABA analogues for use in sleep induction...Gower noted that while LEV was only weakly effective in the more common maximal electric shock (MES) and pentylenetetrazole (PTZ) models, it was surprisingly effective as an anticonvulsant in an audiogenic mouse model...Seletracetam and brivaracetam (BRV) were both synthesized and BRV was chosen as more promising for clinical development based on effectiveness in MES and PTX models as well as the audiogenic mouse model... LEV would not have been discovered if only standard screening models were used. New screening methods may help identify new ASMs.New..."

Absence Seizure Disorder • CNS Disorders • Epilepsy • Movement Disorders • Psychiatry

Olig2-specific Loss-of-Function Slc35a2 Results in Hypomyelination and Spontaneous Seizures (AES 2025) - "Behavioral assessments included neurological scoring, open field, locomotor habituation, and pentylenetetrazole-induced seizure testing in 85 mice (26 female controls, 17 female cKO, 26 male controls, 16 male cKO), aged 4-18 weeks... Our results demonstrate that loss of SLC35A2 function in oligodendrocytes alone is sufficient to reproduce key pathological and clinical features observed in human mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy. Notably, the emergence of spontaneous seizures in the absence of direct neuronal genetic abnormalities highlights a central role for oligodendrocyte dysfunction and hypomyelination in epileptogenesis. These significant findings challenge the traditional neuron-centric view of epilepsy and suggest that targeting glial dysfunction may offer novel therapeutic opportunities."

CNS Disorders • Epilepsy • Solid Tumor • OLIG2 • SLC35A2

Planarian behavioral screening is a useful invertebrate model for evaluating seizurogenic chemicals. (PubMed, bioRxiv) - "We found that known seizurogenic compounds in mammals (NMDA, nicotine, picrotoxin, pilocarpine, and pentylenetetrazole (PTZ)) induced seizure-like behavior in both planarian species within 30 min of exposure. By standardizing both experimental approach and analysis methods and making them available, this work can serve as a framework for future testing of chemicals for seizurogenic potential in planarians. Classic seizurogenic chemicals induce convulsions in planariansA 48-well exposure paradigm allows for rapid testing of seizurogenic compoundsAutomated analysis replaces manual scoring of seizure-like planarian behaviorAcute parathion exposure causes seizure-like activity in planarians."

Journal • CNS Disorders • Epilepsy

DHX9 Aggravates Epilepsy by Promoting STAT1 Phosphorylation to Increase Oxidative Stress and Apoptosis. (PubMed, Brain Res Bull) - "This study reveals the important role of DHX9 in epilepsy pathogenesis and elucidates the molecular mechanism by which DHX9 directly interacts with STAT1 and promotes its phosphorylation, thereby activating downstream oxidative stress and apoptotic signaling pathways, ultimately aggravating epileptic neuronal injury."

Journal • CNS Disorders • Epilepsy • Inflammation • DHX9

Effects of Levetiracetam on hippocampal glutamate transporter 1 loss and dendritic defect in a pentylenetetrazole-induced epilepsy mouse model and drug-resistant epilepsy patients (Neuroscience 2025) - "Finally, analysis of human hippocampal tissue supported the correlation of LEV administration and dendritic histological findings mentioned above. In summary, these results suggest that LEV treatment in an epilepsy animal model has beneficial effects for the preservation of astrocytic glutamate transporters and dendritic integrity, which support its clinical application in improving therapeutic strategies to protect neuroglial functions in patients."

Preclinical • CNS Disorders • Epilepsy • GFAP

Olig2-specific loss-of-function Slc35a2 results in hypomyelination and spontaneous seizures (Neuroscience 2025) - "Behavioral assessments included neurological scoring, open field, locomotor habituation, and pentylenetetrazole-induced seizure testing in 85 mice (26 female controls, 17 female cKO, 26 male controls, 16 male cKO), aged 4-18 weeks...Notably, the emergence of spontaneous seizures in the absence of direct neuronal genetic abnormalities highlights a central role for oligodendrocyte dysfunction and hypomyelination in epileptogenesis. These significant findings challenge the traditional neuron-centric view of epilepsy and suggest that targeting glial dysfunction may offer novel therapeutic opportunities."

CNS Disorders • Epilepsy • OLIG2 • SLC35A2

Synergistic Effect of Cannabidiol and Cannabigerol on Seizures Induced by Pentylenetetrazole (Neuroscience 2025) - "Results showed a statistically significant reduction in the frequency and severity of tonic-clonic seizures in the CBD + CBG + PTZ group. In conclusion, the combination of CBD and CBG appears to exert a synergistic anticonvulsant effect, potentially enhancing neuroprotection against excitotoxic damage and reducing seizure activity."

CNS Disorders • Epilepsy

Disrupted temporal integration in hippocampal ca1 neurons during pentylenetetrazole-induced epileptogenesis. (Neuroscience 2025) - "PTZ-induced epileptogenesis profoundly disrupts temporal integration within the hippocampus, through enhanced presynaptic glutamate release and altered excitatory and inhibitory (E/I) balance. These findings provide mechanistic insights into epileptic network dysfunction and may inform therapeutic strategies targeting temporal coding deficits in epilepsy."

CNS Disorders • Epilepsy

The fast-dissociating D2 antagonist antipsychotic JNJ-37822681 is a neuronal Kv7 channel opener: potential repurposing for epilepsy treatment (Neuroscience 2025) - "These effects were blocked by the Kv7 inhibitor XE-991 and were not replicated by the D2 receptor antagonist (-)-sulpiride, confirming that the observed effects of JNJ-37822681 were specifically mediated via Kv7 channel activation. In vivo, JNJ-37822681 significantly reduced the severity and frequency of pentylenetetrazole-induced seizures in C57BL mice and sound-induced seizures in genetically epilepsy-prone DBA/2 mice, with a potency comparable to retigabine. Pretreatment with XE-991 attenuated the antiseizure effects of JNJ-37822681 in both models, further supporting a Kv7-dependent mechanism of action. Given its favorable safety profile in humans and lack of the chemical liabilities associated with retigabine, JNJ-37822681 represents a compelling candidate for further development of novel ASMs."

CNS Disorders • Epilepsy • DRD2 • KCNQ1OT1

Kr233: selective kcnq2/3 opener with best-in-class potential for epilepsy (Neuroscience 2025) - "Ezogabine (retigabine), the first KCNQ opener approved in 2011 for the treatment of focal seizures, was voluntarily withdrawn from the market in 2017 due to chemical issues unrelated to its action on Kv7.2/3...In preclinical models, KR233 provided robust protection against seizures in both the pentylenetetrazole (PTZ) and maximal electroshock (MES) -induced seizure models, with a good PK/PD correlation (EC50,plasma <50 ng/ml)...In contrast, XEN-1101 induced significant impairments at equivalent doses with TD50 < 40 mg/kg in the same condition...Overall, these results indicate that KR233 is a promising novel therapeutic candidate for the treatment of epilepsy. IND filling expected in Q3 2025."

CNS Disorders • Epilepsy

Anti-convulsant efficacy of long-acting injectable cannabidiol formulation (IVL5005) in the pentylenetetrazol-induced convulsions, with pharmacokinetic characterization. (PubMed, Front Pharmacol) - "Epidiolex®, an FDA-approved oral CBD solution, is indicated for rare epileptic disorders such as Lennox-Gastaut syndrome and Dravet syndrome...The optimized formulation was selected for efficacy evaluation in a pentylenetetrazole (PTZ)-induced convulsion model...No hepatic toxicity was observed with IVL5005, while liver changes were detected in the oral CBD group, likely due to extensive first-pass metabolism. These results indicate that IVL5005 may overcome key limitations of oral CBD and support its further development as a long-acting therapeutic option for epilepsy."

Journal • PK/PD data • CNS Disorders • Epilepsy

Neuroprotective Effects of Ammi visnaga Fruit Hydroalcoholic Extract in a PTZ-Induced Seizure Mouse Model: Emphasis on Neuroinflammatory Pathways. (PubMed, Neurochem Res) - "This study aimed to investigate the neuroprotective, anticonvulsant, anti-inflammatory, and antioxidant properties of Ammi visnaga fruit hydroalcoholic extract in a pentylenetetrazole (PTZ)-induced seizure model in mice, with a particular focus on hippocampal oxidative stress and cytokine modulation. Forty adult male NMRI mice were randomized into Six groups including: both healthy negative control and PTZ + saline control, PTZ-only, phenobarbital-treated, and Ammi visnaga-treated (25, 50, and 100 mg/kg)...Ammi visnaga fruit hydroalcoholic extract demonstrated potent, dose-dependent neuroprotective effects in a PTZ-induced seizure model through dual anti-inflammatory and antioxidative mechanisms. Its ability to suppress IL-6 and TNF-α expression and restore redox balance positions it as a promising adjunctive therapeutic candidate for epilepsy management, especially in drug-resistant cases driven by neuroinflammation and oxidative stress."

Journal • Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Epilepsy • Inflammation • IL6 • TNFA

Discovery of novel hybrid pyrrolidin-2-one derivatives exhibiting potent antiseizure and antinociceptive effects in preclinical models. (PubMed, Biomed Pharmacother) - "In addition, (R)-9 was active in the pentylenetetrazole (PTZ)-induced kindling model as well as in spontaneous electrographic bursting, an in vitro model of pharmacoresistant seizure-like activity at a concentration of 120 μM...Besides its TRPV1 antagonistic activity, (R)-9 effectively inhibited voltage-gated sodium channels at a concentration of 50 μM in electrophysiological studies. Collectively, these findings support the further preclinical development of (R)-9 as a promising candidate for the treatment of epilepsy and pain-related disorders."

Journal • Preclinical • CNS Disorders • Epilepsy • Neuralgia • Pain • TRPV1

Anticonvulsant Activity of 12-Epinapelline N-Oxide, a Diterpene Alkaloid of the Atisine Series. (PubMed, Bull Exp Biol Med) - "The anticonvulsant activity of the diterpene alkaloid 12-epinapelline N-oxide isolated from the aboveground part of Aconitum baicalense was demonstrated in experiments on mice with modeled maximal electroshock-induced seizure and pentylenetetrazol-induced seizures. Taking into account the mechanism of seizure development in the studied models, we can hypothesize that the anticonvulsive activity of the alkaloid is determined by its interaction with Na+ channels and GABAA receptors."

Journal • CNS Disorders • Epilepsy

Brain-targeted intranasal pregabalin niosomes for the treatment and prevention of teratogenic congenital malformations in PTZ-induced seizures in pregnant rats without passing placental barrier. (PubMed, Eur J Pharmacol) - "The study evaluated the efficacy of a niosomal formulation of pregabalin (PGB) in pentylenetetrazole (PTZ)-induced seizures in pregnant rats with acute epileptic-type convulsions. The rats were divided into five groups: (1) a saline-administered negative control group of pregnant rats, (2) a positive control group receiving PTZ (3 doses on the 15th, 17th, and 19th days of pregnancy) without treatment, (3) an oral PGB group also administered PTZ 3X, (4) an intranasal PGB group with PTZ 3X, and (5) a standard-treated group receiving intraperitoneal diazepam (DIAZ plus PTZ 3X)...The niosomal PGB formulation effectively reduced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Bcl-2-associated X protein (BAX) expression in maternal and fetal brain tissues, potentially mitigating embryotoxicity and exhibiting antioxidant, antifibrotic, and anti-inflammatory effects. This protective action may help prevent PTZ-induced seizures, underscoring the..."

IO biomarker • Journal • Preclinical • CNS Disorders • Epilepsy • BAX