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

Cortical Somatostatin Neurons Regulate Seizure Susceptibility via MINAR1/Gαs-cAMP Signaling. (PubMed, Adv Sci (Weinh)) - "During postnatal growth, gross brain morphology and cytoarchitecture were comparable between MINAR1 CKO mice and littermate controls; adult CKO mice exhibited increased vulnerability to pentylenetetrazole (PTZ)-induced seizures, and this phenotype was also present in SST-Cre-mediated CKO mice...Notably, pharmacological activation of adenylate cyclase with forskolin rescued this inhibitory defect. Collectively, our results establish MINAR1 as a key regulator of seizure susceptibility, likely via Gαs-cAMP-dependent modulation of SST+ interneurons, offering a molecular framework for developing targeted epilepsy therapies."

Journal • Breast Cancer • CNS Disorders • Epilepsy • Oncology • Solid Tumor • NOTCH2

A Comprehensive Preclinical Characterization of BMS‑986368, a First-in-Class, Oral, Dual Inhibitor of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase (ACTRIMS Forum 2026) - P2 | "The antiseizure and antiepileptogenic activity of BMS-986368 at 2-30 mg/kg was determined using electroconvulsive shock (ECS) threshold and maximal ECS tests, pentylenetetrazole seizure models, and amygdala electrical kindling models. BMS-986368 is a first-in-class, orally bioavailable, centrally penetrant dual FAAH/MAGL inhibitor with a moderate half-life that was efficacious in rodent seizure and epileptogenic models and well tolerated in CMs for 9 months. BMS-986368 is under phase 2 investigation for the treatment of MS spasticity (BALANCE-MSS-1; NCT06782490) and other neurologic hyperexcitability disorders."

Preclinical • CNS Disorders • Epilepsy • Inflammation • Movement Disorders • Multiple Sclerosis

Neuroprotective Effects of Anodal tDCS on Oxidative Stress and Neuroinflammation in Temporal Lobe Epilepsy. (PubMed, Biomedicines) - " Anodal tDCS exerts neuroprotective effects in acute and chronic epilepsy by modulating oxidative stress, neuroinflammation, and the astrocytic/nitric oxide pathways, supporting its potential as a non-invasive adjunct therapy for cognitive and cellular protection. Future studies should investigate its effects on hippocampal glutamatergic and GABAergic pathways, as well as calcium homeostasis."

Journal • CNS Disorders • Cognitive Disorders • Epilepsy • Inflammation • GFAP • IL1B • TNFA

Potential Effect of Belladonna in the Management of Convulsions in Zebrafish (Danio rerio) and In Silico Mechanistic Approach. (PubMed, Ann Neurosci) - "The effect of homoeopathic Belladonna on pentylenetetrazole (PTZ)-induced seizures in zebrafish (Danio rerio) was assessed in this study...Collectively, these findings support the potential of Belladonna as an anticonvulsant and could be a potential candidate for the management of epilepsy. However, further exploration for epilepsy management through the underlying mechanisms of action is needed in the future."

Journal • CNS Disorders • Epilepsy

Influence of dietary supplementation with two distinct probiotic strains, Bifidobacterium longum R0175 and Lacticaseibacillus rhamnosus JB-1, on seizure susceptibility and valproate response: Behavioral and biochemical studies in mice. (PubMed, Nutrition) - "The probiotics alone had minimal effects on seizure thresholds, but they enhanced the antiseizure efficacy of valproate, which may be linked to increased SCFA production and altered gut metabolism. These findings support further studies on probiotics as a complementary strategy in epilepsy treatment."

Journal • Preclinical • CNS Disorders • Epilepsy • Mood Disorders • Psychiatry

BETMB: A Dual-Target Compound for Synergistic Suppression of Neuronal Hyperexcitability in Refractory Epilepsy via Concurrent Modulation of Nav Channels and GABAA Receptors. (PubMed, CNS Neurosci Ther) - "BETMB is a promising dual-target therapy for refractory epilepsy, supported by the first electrophysiological evidence that dual modulation of GABAAR and NaV synergistically suppresses neuronal hyperexcitability. Beyond epilepsy, this finding may also extend to CSD-related conditions such as stroke, traumatic brain injury, and migraine."

Journal • Cardiovascular • CNS Disorders • Epilepsy • Migraine • Pain • Vascular Neurology

The Effect of Music Exposure on Epileptic Seizures Induced by Pentylenetetrazole in Rats. (PubMed, Med Princ Pract) - "Under the present experimental conditions, Mozart K.448 did not significantly modulate GABAergic activity as measured by PPI. The observed trends toward shorter seizure latency and higher seizure severity in the music group may reflect a possible context-dependent increase in excitability, although these findings remain preliminary due to the small sample size. Given the complex nature of music's effects, further studies employing larger cohorts, and complementary neurophysiological methods are warranted."

Journal • Preclinical • CNS Disorders • Epilepsy

Exploring the Anticonvulsant and Neuropreventive Effects of Ganoderma lucidum Extract in the Pentylenetetrazole-Kindling Model: Analysis of Cognitive Comorbidities Associated with Epilepsy. (PubMed, Neurochem Res) - "Four groups of male Wistar rats were randomly assigned: control, PTZ, GLE-300, and Diazepam, each consisting of 8 rats. Histopathological analysis also confirmed these results. These results indicate that GLE supplementation has therapeutic impacts on cognitive comorbidities and decreases PTZ damage, which may be associated with reduced oxidative stress in the hippocampus."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy • CA3 • CAT

Gut-brain cholinergic signaling mediates the antiseizure effects of Bacteroides fragilis. (PubMed, Neuron) - P=N/A | "fragilis) is markedly reduced in children with epilepsy and show that oral B. fragilis administration suppresses seizures in both pentylenetetrazole- and kainic-acid-induced mouse models...A randomized clinical trial (CHiCTR2100042203) further confirms the therapeutic efficacy of B. fragilis in pediatric refractory epilepsy. These findings define a gut-brain cholinergic pathway through which B. fragilis exerts antiseizure effects and establish a mechanistic basis for microbiota-targeted therapies in epilepsy."

Clinical • Journal • CNS Disorders • Epilepsy • Pediatrics • CHAT

Valproate-Induced Hormonal and Histological Alterations in PTZ-Kindled Female Rats with a Focus on 5HT1A Receptors. (PubMed, Behav Brain Res) - "The results indicate that co-administration of the 5-HT1A receptor antagonist with VPA exacerbated the observed hormonal and ovarian alterations. These findings suggest that 5-HT1A receptor activity may be involved in modulating VPA-associated endocrine and tissue changes, while receptor blockade is associated with increased reproductive adverse effects."

Journal • Preclinical • CNS Disorders • Endocrine Disorders • Epilepsy • Infertility • Sexual Disorders

Walnut peptide and theanine combination ameliorates sleep disorders: a multi-species study including a human trial. (PubMed, Food Funct) - "Treatment with WPT reduced waking activity and duration in pentylenetetrazole (PTZ)-induced zebrafish...In conclusion, this translational study provides robust evidence that the WPT effectively improves chronic stress-induced sleep disorders in zebrafish and mice, and improves sleep disturbances in adults (PSQI ≥ 7) by regulating HPA axis function and restoring the duration and quality of SWS. This makes it a highly promising nutritional intervention strategy."

Journal • CNS Disorders • Sleep Disorder

Novel 7-Substituted-1,2,4-Triazolopyrimidines targeting Nav1.2 channels as low-neurotoxicity antiepileptic agents. (PubMed, Bioorg Med Chem) - "In pursuit of novel antiepileptic agents with improved safety profiles, a series of novel 7-substituted-[1,2,4]triazolo[1,5-a]pyrimidine derivatives were synthesized and evaluated for antiepileptic activity using the subcutaneous pentylenetetrazole (Sc-PTZ) and maximal electroshock seizure (MES) models in vivo...The antiepileptic efficacy of 6c surpassed that of the reference drugs phenytoin and valproate...These results suggest that compound 6c is a promising lead candidate for the development of novel antiepileptic agents with high efficacy and low neurotoxicity. Preliminary in vitro assessment in rat liver microsomes indicated moderate metabolic stability for 6c, supporting its potential for further development."

Journal • CNS Disorders • Epilepsy • NAV1

ZFRA PEPTIDE-ACTIVATED Z CELLS INDUCE NEURAL REGENERATION, SUPPRESS SEIZURES, RESTORE SHORT-TERM MEMORY, AND ENHANCE LOCOMOTION (ADPD 2026) - " The study involved 1) treatment of Wwox wild-type and heterozygous mice with pentylenetetrazole (PTZ) to induce seizures, 2) pre-exposure of mice to Zfra4-10 peptide and mutant peptides to block the development of PTZmediated seizures, 3) isolation of 23 Zfra-binding proteins by protein microarray chip analysis, 4) inhibition of these proteins by specific IgG to suppress seizures and enhance animal behavioral performance, and 5) isolation of Zfraactivated Z cells to block seizures... In summary, Zfra4-10-activated Z cells, via the WWOX/PPIA/CHCHD4/MXD4 signaling suppresses seizures, blocks AD progression, and enhances locomotion in mice. (Supported by NSTC, Taiwan 113-2320-B-039 -006)"

Alzheimer's Disease • CNS Disorders • Epilepsy • NANOG • PPIA • SOX2 • WWOX

Association of Pirfenidone and its Cardioprotective effects in Pentylenetetrazole-induced kindling model of Epilepsy through the High mobility group Box-1/Toll-Like Receptor-4 pathway. (PubMed, Mol Biol Rep) - No abstract available

Journal • CNS Disorders • Epilepsy • Immunology • Inflammation • HMGB1 • TLR4

Metformin attenuates PTZ-Induced seizures and cognitive impairment and is associated with altered NOS/NO signaling: combined in vivo and in silico evidence. (PubMed, Neurol Res) - "Adult male Wistar rats were allocated into control, pentylenetetrazole (PTZ), or metformin+PTZ groups. TargetNet predicted NOS isoforms among potential metformin targets, and docking indicated moderate binding affinity (-5.2 to -5.9 kcal/mol). Metformin exerted seizure-suppressing and cognition-preserving effects in an acute PTZ model, associated with reductions in NOS isoform expression and NO levels, suggesting altered NOS/NO signaling and supporting its potential as an adjunctive candidate for mitigating seizure-related neuronal dysfunction."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy • NOS3

In vivo, in silico effects of sakuranetin as a multi-target nutraceutical against PTZ-induced seizures via GABA restoration and BDNF/TrkB activation. (PubMed, Sci Rep) - "This study evaluated the protective effects of sakuranetin-a flavonoid found in edible Prunus species-against pentylenetetrazole (PTZ)-induced seizures and neurochemical changes in mice...These findings suggest that sakuranetin has substantial, multi-target anticonvulsant effects by restoring neurotransmitter balance, enhancing antioxidant capacity, suppressing neuroinflammation, and revitalizing BDNF/TrkB signaling. Given its dietary origin, sakuranetin warrants further investigation as a potential nutraceutical candidate for managing epilepsy."

Journal • Preclinical • CNS Disorders • Epilepsy • Inflammation • BDNF • CASP3 • CAT • IL1B • IL6 • NTRK2 • TNFA

Transcript Imbalance from TENM4 Exon Skipping: Effects on Epilepsy and Genetic Pleiotropy. (PubMed, Mol Neurobiol) - "Homozygous Tenm4ΔE10/ΔE10 mice exhibited significantly increased susceptibility to pentylenetetrazole-induced seizures...An imbalance in the proportion can impair oligodendrocyte development, causing structural brain abnormalities and seizure susceptibility. In conclusion, our findings successfully elucidated a novel pathomechanism that emphasized the role of transcript isoform imbalance in neurodevelopmental diseases and expanded the pleiotropic condition of TENM4."

Journal • CNS Disorders • Developmental Disorders • Epilepsy • Essential Tremor • Mental Retardation • Movement Disorders • Psychiatry • Schizophrenia • Solid Tumor • TENM4

Retraction Notice: Anti-kindling Effect of Bezafibrate, a Peroxisome Proliferator-activated Receptors Alpha Agonist, in Pentylenetetrazole Induced Kindling Seizure Model. (PubMed, J Epilepsy Res) - "[This retracts the article on p. 45 in vol. 4, PMID: 25625088.]."

Journal • CNS Disorders • Epilepsy

Chlorogenic acid exerts anti-inflammation and neuroprotective effect in pentylenetetrazole-induced epilepsy mouse model by regulating microglia polarization via Nrf2/HO-1 pathway. (PubMed, Neurosci Lett) - "Finally, western blot analysis indicated the activation of the Nrf2/HO-1 pathway, and Nrf2 knockdown reversed CGA's effects. These findings suggest that CGA exerts anti-seizure and neuroprotective effects via microglial modulation through the Nrf2/HO-1 pathway."

Journal • Preclinical • CNS Disorders • Epilepsy • Inflammation

Anticonvulsant biotargets of digoxin: in silico study and in vivo verification. (PubMed, Ceska Slov Farm) - "To confirm the in silico results in vivo pharmacological studies under conditions of acute bicuculline-induced seizures and pentylenetetrazole kindling in mice have been carried out. It was established that digoxin shows high affinity to GABAergic biotargets and an identical to retigabine affinity to voltage-gated potassium channels KCNQ2 in silico...At the same time, the ability of digoxin to maximally enhance the anticonvulsant potential of sodium valproate has been revealed. Thus, it has been proven that the anticonvulsant properties of digoxin are most likely related to the ability to enhance the inhibitory properties of GABA and GABAergic agents."

Journal • Preclinical • CNS Disorders • Epilepsy

Brivaracetam Combined With Topiramate at Low Doses Alleviates Neurobehavioral Deficits and Oxidative Stress in a Chemoconvulsant Kindled Seizure Model. (PubMed, Behav Neurol) - "This study examined the therapeutic effect of topiramate (TPM) and brivaracetam (BRV), both separately and combined, using pentylenetetrazole-kindled mice. Biochemically, the combined treatment restored antioxidant enzyme levels (SOD, CAT, and GPx) by 45%-70% and significantly lowered MDA levels (70.7%) and restored SOD activity (220.9%). These findings suggest that low-dose rational polytherapy with TPM and BRV may enhance seizure control and ameliorate associated neuropsychiatric and oxidative imbalance."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Depression • Epilepsy • Mood Disorders • Psychiatry

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