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

Visual exposure to seizure-like behavior induces social disengagement without stress contagion in zebrafish (Neuroscience 2026) - "Demonstrators received either reverse-osmosis water or pentylenetetrazole (PTZ), a convulsant that induces seizure-like behavior, while both demonstrator and observer behavior were simultaneously quantified...These findings indicate that pathological motor disturbance is insufficient to induce behavioral or endocrine stress contagion in zebrafish despite producing a robust demonstrator phenotype, contrasting with previous studies using ethologically relevant antipredator cues. The results support a cue-dependent model of affective state transmission in which emotional contagion depends on the interpretation of biologically relevant social signals rather than generalized sensitivity to abnormal conspecific behavior."

CNS Disorders • Epilepsy

Influence of Chronic-Depression Models and SSRI Treatment on Vulnerability to Pentylenetetrazole-Induced Seizures in Rats (Neuroscience 2026) - "Depressive-like behavior was induced using two models, Chronic Unpredictable Stress (CUS) and Social Isolation (SI), concomitant with treatment with fluoxetine (FLX) or citalopram (CIT) (10 mg/kg, s.c.) for 21 days. These findings suggest that stress-induced alterations modulate the thalamocortical circuitry involved in the generation of paroxysmal activity. Furthermore, SSRIs administered at doses effective in reducing depressive-like behaviors did not exacerbate epileptiform activity, supporting their safety and efficacy in young adults with acute epilepsy."

Preclinical • Absence Seizure Disorder • CNS Disorders • Depression • Epilepsy • Major Depressive Disorder • Mood Disorders • Psychiatry

Novel synthetic neurosteroid PPG offers distinctive mechanisms of anti-seizure protection in the pentylenetetrazol animal model of limbic epilepsy. (Neuroscience 2026) - "We used simultaneous two-photon calcium imaging and single-channel electrocorticography (ECoG) to compare a newly developed synthetic neurosteroid pregnanolone pyroglutamate (PPG) with lorazepam under physiological conditions and during pentylenetetrazole (PTZ)-induced seizures. Finally, a subsequent experiment showed that PPG prevented seizures even when PTZ was given at a supralethal dose of 150 mg/kg, whereas lorazepam only prevented death. PPG reduced cortical excitatory neuronal activity and maintained network effects during PTZ challenge, supporting further evaluation of synthetic neurosteroids as candidate therapies for pharmacoresistant epilepsy."

Preclinical • CNS Disorders • Epilepsy

Effect of Cannabidiol and Cannabigerol on Nitric Oxide Production in a Pentylenetetrazole-Induced Seizure Model (Neuroscience 2026) - "Regarding nitrite levels, treatment with CBG+CBD/PTZ induced changes in nitrite concentrations, particularly in the cerebellum. These findings suggest that CBD and CBG exert a regulatory effect on nitric oxide production and reduce seizure activity in the PTZ model."

CNS Disorders • Epilepsy

Efficacy of chitosan-encapsulated carbamazepine on seizures induced by pentylenetetrazole kindling. (PubMed, Neurosci Lett) - "Characterization of the optimized nanoparticles revealed a mean particle size of 65 nm, a polydispersity index (PDI) of 0.21, a zeta potential of -34.5 mV, and an entrapment efficiency of 55.35 %, indicating favorable stability and delivery properties. Overall, this study demonstrates that chitosan‑based nanoencapsulation of carbamazepine enhances its antiepileptic efficacy in a PTZ‑kindling model, suggesting its promise as a potential therapeutic strategy for epilepsy."

Journal • CNS Disorders • Epilepsy

Multifocal Initiation of Spreading Depolarization by Generalized Tonic-Clonic Seizures. (PubMed, Int J Mol Sci) - "Using a pentylenetetrazole seizure model and in vivo electrophysiology, we examined the occurrence of SD in different regions of the cortex and hippocampus in response to acute tonic-clonic seizures in freely behaving rats...Our findings support the idea that the awake brain rapidly responds to acute generalized seizures with multifocal initiation of SD in the cortex and hippocampus. We suggest that the seizure-induced SD contributes to seizure termination in the cortex but not in the hippocampus."

Journal • CNS Disorders • Depression • Epilepsy • Psychiatry

Design, synthesis, in vivo, and in silico evaluation of novel quinoline-based dihydrothiazoles as anticonvulsants. (PubMed, J Comput Aided Mol Des) - "The in vivo anticonvulsant activity was assessed using an acute chemoconvulsant model, where seizures were induced by a single dose of pentylenetetrazole (PTZ 80 mg/kg)...Based on in vivo findings, compounds 3d and 3i emerged as the most potent candidates, demonstrating superior anticonvulsant activity in comparison with the standard reference drugs. Molecular docking against the GABA-A receptor additionally identified 3 g as the top computational binder, which is discussed as a complementary in silico finding along with experimentally validated lead."

Journal • Preclinical • CNS Disorders • Epilepsy

Neuronal Activity Rapidly Decreases the Level of p53 Protein in Rat Hippocampus In Vivo. (PubMed, Bull Exp Biol Med) - "To answer this question, we employed a pentylenetetrazole (PTZ)-induced seizure model in rats. At 20 and 40 min after an intraperitoneal injection of PTZ, hippocampal p53 levels were significantly reduced compared to the intact controls. These findings validate the data previously obtained in vitro."

Journal • Preclinical • CNS Disorders • Epilepsy • Oncology • TP53

Toxicological profile and neuromodulatory effects of a secoiridoid-rich extra-virgin olive oil extract in a zebrafish model of chemically induced seizures. (PubMed, Biomed Pharmacother) - "In summary, EVOO-NaDES extract pre-treatment modulates PTZ-associated locomotor responses alongside correlated changes in selected transcriptional markers. Rather than establishing definitive functional mechanisms, this study provides a hypothesis-generating basis for candidate molecular targets, while the active vehicle and lack of electrophysiological validation preclude attributing these effects strictly to antiseizure activity."

Journal • CNS Disorders • Epilepsy • BDNF • NOS1

Empagliflozin attenuates PTZ-induced neurotoxicity and enhances the protective effects of levetiracetam: associations with NRF2/GPX4 and AMPK/ULK1/ LC3-II signaling. (PubMed, Neurotoxicology) - "EMPA was associated with antiseizure and neuroprotective effects in PTZ-induced kindling epilepsy, particularly when combined with reduced-dose LEV (100mg/kg). These findings suggest that EMPA may represent a promising candidate for further investigation as an adjunctive therapeutic approach in epilepsy."

Journal • CNS Disorders • Epilepsy • GPX4 • MAP1LC3B • ULK1

High frequency stimulation in thalamic reticular nucleus blocks the effect of pentylenetetrazole. (PubMed, Brain Res) - "The results suggest that the TRN participates in the maintenance of characteristic spike-wave discharges, while HFS in the TRN can inhibit the synchronization of oscillatory activity. In conclusion, HFS in the TRN may block burst firing in the TRN and may be sufficient to protect against the spread of convulsive seizures."

Journal • Anesthesia • CNS Disorders • Epilepsy

Cue-dependent limits of stress contagion in zebrafish: visual exposure to seizure-like behavior alters social positioning without stress transfer. (PubMed, Behav Brain Res) - "Demonstrator zebrafish were administered pentylenetetrazole (PTZ), a convulsant that induces seizure-like behavior, while naïve observers viewed them from an adjacent tank...Thus, visual exposure to a conspicuous, physiologically stressful, non-ethological conspecific disturbance was insufficient to produce the canonical behavioral and endocrine pattern of stress contagion measured here. The dissociation between altered social-spatial organization and canonical stress responses identifies a boundary condition for affective-state transmission and is consistent with the hypothesis that zebrafish stress contagion depends on the structure, modality, and biological relevance of social cues."

Journal • CNS Disorders • Epilepsy

Bi-allelic GAD2 variants cause a rare developmental encephalopathy with early-onset seizures. (PubMed, Genet Med) - "Our findings firmly establish GAD2 as a disease gene implicated in developmental encephalopathy with early-onset seizures. The concordance between the human phenotype and the characteristics of the knockout mouse model emphasizes the pivotal role of GAD2 in neurodevelopment and epilepsy."

Journal • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • Mental Retardation • Mood Disorders • Psychiatry

A stereotaxic surgical protocol for posterior and total corpus callosotomy in adult Wistar rats using the WIN-PTZ kindling model. (PubMed, MethodsX) - "The protocol encompasses: (1) a validated seven-session pentylenetetrazole (PTZ) kindling schedule (37.5 mg/kg, i.p., alternating days); (2) a complete multimodal anesthesia and analgesia regimen; (3) precise stereotaxic coordinates for both procedures, referenced from bregma using the Paxinos and Watson rat brain atlas; and (4) a postoperative PTZ rechallenge paradigm with behavioral outcome assessment using the revised Racine scale...On hematoxylin-eosin and toluidine blue sections, representative specimens showed morphological features of an in vivo callosal lesion (hemorrhage and reactive gliosis with a mononuclear infiltrate) within the transected territory, although prolonged fixation compromised tissue quality and precluded evaluation of the transection in many specimens. The protocol therefore supports feasibility, procedural repeatability, and preliminary morphological evidence of callosal disconnection, while confirmation of myelinated-fiber interruption at the..."

Journal • Preclinical • Anesthesia • CNS Disorders • Epilepsy • Hematological Disorders

Dual-acting flavonol analogues as cholinesterase inhibitors and anticonvulsant agents: integrated in vitro, in vivo, and in silico studies. (PubMed, RSC Adv) - "Selected derivatives demonstrating significant enzyme inhibition were further assessed for anticonvulsant efficacy in maximal electroshock seizure (MES) and pentylenetetrazole (PTZ)-induced seizure models...The convergence of biological and computational findings identified compound 8 as the most promising multifunctional candidate, exhibiting potent dual cholinesterase inhibition, pronounced anticonvulsant activity, and sustained target engagement. These results demonstrate that flavonol-based scaffolds represent attractive lead structures for the development of multifunctional therapeutic agents targeting neurodegenerative disorders and epilepsy."

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

Gastrodia elata Blume and Acorus tatarinowii Schott mixtures alleviate pentylenetetrazol-induced seizures in mice: association with NLRP3 inflammasome signaling changes. (PubMed, J Pharm Pharmacol) - "GEAT exerts multi-target effects against epilepsy, associated with synergistic regulation of glial activation, neuroinflammation, and apoptosis involving the NLRP3/caspase-1/IL-1β pathway, thereby providing a robust theoretical and experimental foundation for its clinical translation."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy • Inflammation • Mood Disorders • Psychiatry • BDNF • CASP8 • IL1B • NLRP3

Antidepressant-like and Anticonvulsant Effects of a Phenolic-Enriched Fraction from Malpighia mexicana in Murine Models. (PubMed, NeuroSci) - "However, since only the G4 fraction was pharmacologically evaluated and not the isolated compounds, the specific role of each constituent remains to be established. Further studies are required to elucidate the underlying mechanisms of action and the contribution of individual compounds and potential synergistic interactions."

Journal • Preclinical • CNS Disorders • Epilepsy

Retraction Note: Thymoquinone and Vitamin C Attenuates Pentylenetetrazole-Induced Seizures Via Activation of GABAB1 Receptor in Adult Rats Cortex and Hippocampus. (PubMed, Neuromolecular Med) - No abstract available

Journal • Preclinical • CNS Disorders • Epilepsy

Bioactivity-guided Isolation of Anticonvulsant and Anxiolytic Constituents from Stachys and Teucrium species. (PubMed, J Ethnopharmacol) - "The findings provide experimental evidence supporting the traditional use of S. byzantina in neurological disorders and identify chlorogenic acid as a major bioactive constituent contributing to its anticonvulsant activity. These results highlight the therapeutic potential of S. byzantina as a source of plant-derived anticonvulsant and neuroprotective agents and warrant further pharmacological and mechanistic investigations."

Journal • CNS Disorders • Epilepsy • Mood Disorders • Psychiatry

Genetic and stochastic basis of phenotypic discordance in 16p11.2 mouse model deletion. (PubMed, bioRxiv) - "Using electrocorticography experiments, we detected that approximately 50% of the isogenic del/+ mice exhibited increased susceptibility to seizures from low doses of the convulsant drug pentylenetetrazole (PTZ)...Seizure-prone del/+ mice exhibited reduced activity-dependent immediate early gene signatures and coordinated changes in regulatory programs, including decreased expression of transcriptional regulators and metabotropic glutamate receptor genes, compared to low responders. Together, these findings define two distinct adult del/+ subgroups with convergent circuit, structural, behavioral, and molecular signatures."

Journal • Preclinical • CNS Disorders • Developmental Disorders • Epilepsy • Psychiatry • Sleep Disorder • FOS

Photosensitive response mouse model: A potential tool for studying mechanisms of photosensitive epilepsy and initial screening of anti-epileptic drugs. (PubMed, J Physiol) - "By modulating the luminance within the behavioural chamber we found that the response amplitude diminished with reduced stimulus contrast...Acute treatment with pentylenetetrazole (PTZ) enhanced the photosensitive response in V1, whereas chronic PTZ treatment did not...The photosensitive response can propagate to the medial prefrontal cortex (mPFC) region but does not induce clinical epileptic seizures. Some anti-epileptic drugs can alleviate the photosensitive response."

Journal • Preclinical • CNS Disorders • Epilepsy

Cenobamate and Trazodone Combination Suppresses Seizures, EEG Alterations, Preserves Neuronal Architecture and Normalizes the BDNF/TrkB Expression in PTZ‑Kindled Mice. (PubMed, Neurochem Res) - "Therefore, we investigated the effect of cenobamate (CNB, 30 mg/kg) and trazodone (TZ, 10 mg/kg), alone and in combination, in PTZ-kindling model, where mice received 11 doses of pentylenetetrazole (PTZ, 40 mg/kg) every other day for three weeks. These parallel findings suggest that positive allosteric GABAA modulation and persistent sodium-current inhibition by CNB, combined with TZ serotonergic modulation, reduce hyperexcitability, pathological neuroplasticity, and glial reactivity. Collectively, TZ + CNB is a promising mechanistically complementary regimen that suppresses seizure progression and associated molecular and neurostructural pathology, which needs further preclinical optimization and translational investigations."

Journal • Preclinical • CNS Disorders • Epilepsy • BDNF • GFAP • NTRK2

Comparative effects of posterior versus total corpus callosotomy in a PTZ-induced rat model of epilepsy: a methodological pilot study. (PubMed, Exp Brain Res) - "This pilot evaluated the acute behavioural effects of PC versus TC in a pentylenetetrazole (PTZ) kindling rat model...Neither technique produced statistically detectable acute changes in PTZ-evoked seizure duration; given the pilot's limited sensitivity, the findings are exploratory and hypothesis-generating. Because PTZ generalization depends largely on subcortical pathways, this model appears suboptimal for isolating callosal contributions; adequately powered studies in chronic focal epilepsy models, with electrophysiological monitoring and longer follow-up, are needed."

Clinical • Journal • Preclinical • CNS Disorders • Epilepsy

β-hydroxybutyrate regulates microglia M1/M2 polarization and phagocytosis through the JAK1/STAT1 pathway to reduce neuroinflammation and exert anti-epileptic effects. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "A rat model of Pentetrazol (PTZ)-induced EP was constructed to detect the effects of BHB on the symptoms of EP in rats by behavioral assessment, and to detect brain tissue damage by pathological staining. Furthermore, BHB was also effective in promoting microglia M2 polarization and enhancing their phagocytosis in vivo. Overexpression of JAK1 attenuated the neuroprotective effects of BHB, and Fludarabine attenuated the impacts of overexpression of JAK1. By inhibiting the JAK1/STAT1 pathway, BHB promotes microglia M2 polarization and enhances their phagocytosis, attenuates neuroinflammation and neuronal injury, and ultimately exerts anti-EP effects."

Journal • CNS Disorders • Epilepsy • Inflammation • JAK1

Pentylenetetrazole kindling impairs place recognition memory associated with suppressing proBDNF-mediated neural information flows at the hippocampal CA3-CA1 synapses. (PubMed, Front Pharmacol) - "This was evidenced by increased spontaneous excitatory postsynaptic current frequency and amplitude, and further corroborated by action potential-independent miniature EPSC (mEPSC) recordings, which revealed concurrent increases in both mEPSC frequency and amplitude specifically in the epilepsy group. However, blocking proBDNF or inactivation of the p75NTR signaling could effectively enhance the phase-locked value and neural information flow at the gamma and high-frequency oscillations, and significantly alleviate the PTZ-induced impairments in memory processing. Our findings are consistent with the hypothesis and provide the first direct evidence that the over-activation of proBDNF signaling represents a potential mechanism involved in neural dysfunction and NIF disruption leading to memory impairments in kindled animals."

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