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

Immunomodulatory and neuroprotective effects of HEPPP in mice with status epilepticus (IMMUNOLOGY 2026) - "In this study, we evaluated whether DL-3-hydroxy-3-ethyl-3-phenylpropionamide (HEPP), an effective drug in refractory epilepsy, presents an immunomodulatory effect on microglia cells in a murine model of pentylenetetrazole (PTZ)-induced status epilepticus. Three groups of five C57BL/6 mice were formed: control, epileptic untreated, and epileptic treated with HEPP... Our findings suggest that HEPP not only modulates seizure activity but also provides immunomodulatory and neuroprotective effects, positioning itself as a promising therapeutic alternative for epilepsy associated with chronic inflammation."

Immunomodulating • Preclinical • CNS Disorders • Epilepsy • Inflammation • IL4 • IL6 • MRC1 • TNFA

Chronic pinacidil attenuates the pentylenetetrazole‑induced kindling in rats. (PubMed, Acta Neurobiol Exp (Wars)) - "Biochemical data showed that chronic pinacidil did not provoke changes in serum creatinine and urea levels or in aspartate aminotransferase and alanine aminotransferase levels. These findings suggest that long‑term administration of pinacidil impairs the progression of PTZ‑induced kindling without causing nephrotoxic or hepatotoxic effects."

Journal • Preclinical • CNS Disorders • Epilepsy

Band gap energy shift as a biophysical marker of Puerarin's neuroprotective role in epilepsy-induced demyelination. (PubMed, J R Soc Interface) - "The study aims to determine the neuroprotective effect of Puerarin, extracted from Pueraria lobata roots, against pentylenetetrazole (PTZ)-induced epileptic seizures and concomitant demyelination and low conductance through diffuse reflectance spectroscopic (DRS) technique...Haematoxylin and eosin and Nissl staining were used to further authenticate the neuroprotective effect of Puerarin. In conclusion, Puerarin countered demyelination and low conductance of nerve owing to PTZ-induced epilepsy assessed via DRS."

Journal • CNS Disorders • Epilepsy • Solid Tumor

Design, Synthesis, and Evaluation of Voltage-gated Sodium Channel Inhibitors as Anticonvulsant Agents. (PubMed, Curr Neurovasc Res) - "All the synthesized acylurea derivatives possess comparable activity to the standard drug. Thus, it can be concluded that the synthesized analogs are potential candidates for further investigation."

Journal • CNS Disorders • Epilepsy

Pretreatment With Methylene Blue Atenuates Seizures, Cognitive Impairment, Hippocampal Neuronal Damage and Oxidative Stress in Pentylenetetrazole-Kindled Rats. (PubMed, Mol Neurobiol) - "Methylene blue demonstrates significant antiseizure and neuroprotective effects in a PTZ-induced epilepsy model. It likely alleviates seizure severity, protects hippocampal neurons and ameliorates cognitive dysfunction by mitigating oxidative stress, providing a strong experimental basis for its potential clinical use in treating epilepsy and its associated comorbidities."

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

DDX3 inhibits PTZ-induced ferroptosis in human neuronal SH-SY5Y cells via Wnt/β-catenin signaling. (PubMed, In Vitro Cell Dev Biol Anim) - "This study aimed to investigate the potential mechanism of DDX3 in pentylenetetrazole (PTZ)-induced ferroptosis in human neuronal SH-SY5Y cells...Our results suggested that DDX3 inhibited PTZ-induced ferroptosis in SH-SY5Y cells through activation of Wnt/β-catenin signaling. Our findings may provide new molecular targets for the treatment of neuropathic diseases."

Journal • ACSL4 • AXIN2 • CCND1 • GPX4 • LEF1 • MMP7 • MYC

Multi-target neuroprotection of carbon dots derived from Crinis Carbonisatus in multiple acute epilepsy model. (PubMed, Front Mol Biosci) - "To evaluate their antiepileptic potential, acute epilepsy models were established in mice using three distinct chemoconvulsants: Pentylenetetrazole (PTZ), Pilocarpine (PILO), and Penicillin (PNC). This study confirms that bio-derived CrCi-CDs exhibit potent antiepileptic and neuroprotective properties. By simultaneously targeting neurotransmission, inflammation, and oxidative stress, CrCi-CDs emerge as a highly promising therapeutic candidate with a favorable safety profile, providing a scientific rationale for the development of biomass-derived nanomedicines in epilepsy management."

Journal • Cardiovascular • CNS Disorders • Epilepsy • Hematological Disorders • Inflammation • Ischemic stroke • IL18 • IL1B • IL6 • TNFA

Synthesis of New Substituted 5H-Benzo[e]imidazo[1,2-a][1,4]diazepines via Pictet-Spengler Reaction and Their Neuroprotective and Anticonvulsant Evaluation. (PubMed, ACS Chem Neurosci) - "In pentylenetetrazole (PTZ)-treated cells, 8b, 8c, and 8e exerted neuroprotective effects by increasing cell viability and reducing ROS levels. The binding analysis at the GABAA site, using molecular docking and MD simulations, suggested a neuroprotective effect of these compounds via GABAA targeting. In vivo, compound 8b demonstrated a dose-dependent anticonvulsant effect in the PTZ-induced kindling mouse model, significantly delaying seizure onset while reducing the seizure duration, frequency, and severity with efficacy comparable to that of diazepam."

Journal • CNS Disorders • Epilepsy

Design, synthesis and anticonvulsant evaluation of novel 2,4,5-trichlorobenzenesulfonate-based dihydrothiazoles supported by in vivo and in silico studies. (PubMed, RSC Adv) - "In the pentylenetetrazole (PTZ) chemoconvulsant model, compound 3c at 150 mg kg-1 showed complete protection from death and hind limb extension...Based on both in vivo and in silico findings, compound 3c emerged as the most important candidate, demonstrating superior anti convulsant activity across multiple seizure models. These results underscore the capability of the newly synthesized 2, 4, 5-trichlorobenzenesulfonate based dihydrothiazoles as promising scaffolds for the development of new antiepileptic drugs."

Journal • Preclinical • CNS Disorders • Epilepsy

Excavating Precursors from the Traditional Chinese Pair Herbs Polygala tenuifolia and Gastrodia elata: Synthesis, Anticonvulsant Activity Evaluation of 3,4,5-Trimethoxycinnamic Acid (TMCA) Peptide Analogs. (PubMed, Pharmaceuticals (Basel)) - "The anticonvulsant activity of all TMCA analogs was evaluated using two acute seizure models in mice: the maximal electroshock (MES) and the sc-pentylenetetrazole (PTZ) models...Compounds 19 and 23 also played roles in controlling the onset of epilepsy in EEG, modulating levels of GABA aminotransferase (GABA-AT)/gamma-aminobutyric acid type A receptor (GABAAR), interacting with active sites of GABA-AT and GABAAR obtained from docking simulation methods. Novel derivatives in this study provide new cores for further design and optimization inspired by TCM herb pair drugs P. tenuifolia and G. elata, with the aim of exploring new anticonvulsant agents."

Journal • CNS Disorders • Epilepsy

Planarian behavioral screening is a useful invertebrate model for evaluating seizurogenic chemicals. (PubMed, Neurotoxicology) - "We found that known seizurogenic compounds in mammals (NMDA, nicotine, picrotoxin, pilocarpine, and pentylenetetrazole (PTZ)) induced seizure-like behavior in both planarian species within 30minutes of exposure. dorotocephala planarians were generally more sensitive, but D. japonica planarians displayed more reproducible behaviors. 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."

Journal • CNS Disorders • Epilepsy

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 PTZ- mediated 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 Zfra- activated 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

Stathmin 1 regulates epileptic seizures by influencing GABAA R-mediated inhibitory synaptic activity. (PubMed, Neurobiol Dis) - "STMN1 downregulation decreased the susceptibility to epileptic seizures in a kainic acid-induced model and pentylenetetrazole-induced kindling model of epilepsy, whereas the overexpression of STMN1 showed opposite effects. More specifically, whole-cell patch-clamp recordings indicate that STMN1 regulated inhibitory synaptic transmission, potentially due to STMN1-mediated postsynaptic GABAAR transport. These results provides the demonstration that STMN1 plays a critical role in the regulation of epileptic seizures, suggesting a molecular mechanism for new therapeutic strategies."

Journal • CNS Disorders • Epilepsy • STMN1

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

Perivascular macrophage depletion impairs glymphatic clearance and amplifies cortical hyperexcitability: Preclinical insights with clinical validation. (PubMed, J Cereb Blood Flow Metab) - "Using clodronate liposomes (CLOs), we achieved >85% PVM depletion in mice. Following pentylenetetrazole (PTZ) challenge, PVM-depleted mice exhibited anxiety-like behaviors (reduced center time, p < 0.05), impaired working memory (decreased spontaneous alternation, p < 0.05), and increased cortical hyperexcitability, including shorter seizure latency and elevated EEG total power (p < 0.05)...These results highlight PVMs as essential modulators of the glymphatic-metabolic axis, linking vascular health to brain excitability. Targeting the PVM-GS interface offers therapeutic potential for disorders involving vascular dysfunction and neuronal hyperexcitability."

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

Validates blood pressure control for seizure management: Jujuboside B exerts antiseizure effects via blood pressure reduction and activation of NTS-VGLUT2+ neurons. (PubMed, Phytomedicine) - "JuB exerts its antiseizure effect through the activation of vagal-mediated NTS-VGLUT2+ neurons and the inhibition of DG neurons. This reconciles cardiovascular and neurological modulation. These findings elucidate JuB's pharmacological basis, advance epileptic pathophysiology understanding, and support personalized therapeutic strategies for epilepsy with hypertension."

Journal • Cardiovascular • CNS Disorders • Epilepsy • Hypertension • FOS

The Application of Copper Nanoparticles Green Formulated by Boswellia thurifera in the Treatment of Epilepsy. (PubMed, J Biomed Mater Res B Appl Biomater) - "The effectiveness of the nanoparticles in producing maximal electroshock (MES) and convulsions induced by pentylenetetrazole (PTZ) was next assessed...Notably, a higher dosage of the nanocomposite and diazepam successfully prevented convulsions in all anticonvulsant studies...These results suggest that CuNPs@B. thurifera has potent anticonvulsant effects, possibly due to its capacity to increase GABA levels in the brain."

Journal • CNS Disorders • Epilepsy

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

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