{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T06:09:29Z","timestamp":1771654169718,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T00:00:00Z","timestamp":1638489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Center","doi-asserted-by":"publisher","award":["UMO-2015\/18\/E\/NZ7\/00509"],"award-info":[{"award-number":["UMO-2015\/18\/E\/NZ7\/00509"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We report herein a series of water-soluble analogues of previously described anticonvulsants and their detailed in vivo and in vitro characterization. The majority of these compounds demonstrated broad-spectrum anticonvulsant properties in animal seizure models, including the maximal electroshock (MES) test, the pentylenetetrazole-induced seizure model (scPTZ), and the psychomotor 6 Hz (32 mA) seizure model in mice. Compound 14 showed the most robust anticonvulsant activity (ED50 MES = 49.6 mg\/kg, ED50 6 Hz (32 mA) = 31.3 mg\/kg, ED50scPTZ = 67.4 mg\/kg). Notably, it was also effective in the 6 Hz (44 mA) model of drug-resistant epilepsy (ED50 = 63.2 mg\/kg). Apart from favorable anticonvulsant properties, compound 14 revealed a high efficacy against pain responses in the formalin-induced tonic pain, the capsaicin-induced neurogenic pain, as well as in the oxaliplatin-induced neuropathic pain in mice. Moreover, compound 14 showed distinct anti-inflammatory activity in the model of carrageenan-induced aseptic inflammation. The mechanism of action of compound 14 is likely complex and may result from the inhibition of peripheral and central sodium and calcium currents, as well as the TRPV1 receptor antagonism as observed in the in vitro studies. This lead compound also revealed beneficial in vitro ADME-Tox properties and an in vivo pharmacokinetic profile, making it a potential candidate for future preclinical development. Interestingly, the in vitro studies also showed a favorable induction effect of compound 14 on the viability of neuroblastoma SH-SY5Y cells.<\/jats:p>","DOI":"10.3390\/ijms222313092","type":"journal-article","created":{"date-parts":[[2021,12,5]],"date-time":"2021-12-05T21:01:45Z","timestamp":1638738105000},"page":"13092","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Identification of New Compounds with Anticonvulsant and Antinociceptive Properties in a Group of 3-substituted (2,5-dioxo-pyrrolidin-1-yl)(phenyl)-Acetamides"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9738-3359","authenticated-orcid":false,"given":"Micha\u0142","family":"Abram","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcin","family":"Jakubiec","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0190-1682","authenticated-orcid":false,"given":"Anna","family":"Rapacz","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3072-8890","authenticated-orcid":false,"given":"Szczepan","family":"Mogilski","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9247-2598","authenticated-orcid":false,"given":"Gniewomir","family":"Latacz","sequence":"additional","affiliation":[{"name":"Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bart\u0142omiej","family":"Szulczyk","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics, Centre for Preclinical Research and Technology, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma\u0142gorzata","family":"Szafarz","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Physical Pharmacy, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7706-2080","authenticated-orcid":false,"given":"Katarzyna","family":"Soca\u0142a","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology and Pharmacology, Institute of Biological Sciences, Maria Curie-Sk\u0142odowska University, Akademicka 19, 20-033 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorota","family":"Nieoczym","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology and Pharmacology, Institute of Biological Sciences, Maria Curie-Sk\u0142odowska University, Akademicka 19, 20-033 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"El\u017cbieta","family":"Wyska","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Physical Pharmacy, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5389-0241","authenticated-orcid":false,"given":"Piotr","family":"Wla\u017a","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology and Pharmacology, Institute of Biological Sciences, Maria Curie-Sk\u0142odowska University, Akademicka 19, 20-033 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafa\u0142 M.","family":"Kami\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2103-371X","authenticated-orcid":false,"given":"Krzysztof","family":"Kami\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,3]]},"reference":[{"key":"ref_1","first-page":"195727","article-title":"Drug Solubility: Importance and Enhancement Techniques","volume":"2012","author":"Savjani","year":"2012","journal-title":"ISRN Pharm."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1007\/s11095-006-0162-4","article-title":"Oral Absorption of Poorly Water-Soluble Drugs: Computer Simulation of Fraction Absorbed in Humans from a Miniscale Dissolution Test","volume":"23","author":"Takano","year":"2006","journal-title":"Pharm. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.2174\/138161209788682479","article-title":"Drug-like Property Concepts in Pharmaceutical Design","volume":"15","author":"Di","year":"2009","journal-title":"Curr. Pharm. Des."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.drudis.2011.11.007","article-title":"Bridging Solubility between Drug Discovery and Development","volume":"17","author":"Di","year":"2012","journal-title":"Drug Discov. Today"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1124\/pr.112.005660","article-title":"Strategies to Address Low Drug Solubility in Discovery and Development","volume":"65","author":"Williams","year":"2013","journal-title":"Pharmacol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1021\/acschemneuro.0c00257","article-title":"Multitargeted Compounds Derived from (2,5-Dioxopyrrolidin-1-Yl)(Phenyl)-Acetamides as Candidates for Effective Anticonvulsant and Antinociceptive Agents","volume":"11","author":"Abram","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1111\/epi.16669","article-title":"KA-104, a New Multitargeted Anticonvulsant with Potent Antinociceptive Activity in Preclinical Models","volume":"61","author":"Mogilski","year":"2020","journal-title":"Epilepsia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"104751","DOI":"10.1016\/j.bioorg.2021.104751","article-title":"Asymmetric Synthesis and in Vivo\/in Vitro Characterization of New Hybrid Anticonvulsants Derived from (2,5-Dioxopyrrolidin-1-Yl)Phenylacetamides","volume":"109","author":"Abram","year":"2021","journal-title":"Bioorganic Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"104557","DOI":"10.1016\/j.bioorg.2020.104557","article-title":"Research Progress in Biological Activities of Succinimide Derivatives","volume":"108","author":"Zhao","year":"2021","journal-title":"Bioorganic Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"111736","DOI":"10.1016\/j.ejmech.2019.111736","article-title":"Synthesis and Biological Evaluation of New Multi-Target 3-(1H-Indol-3-Yl)Pyrrolidine-2,5-Dione Derivatives with Potential Antidepressant Effect","volume":"183","author":"Chodkowski","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"103662","DOI":"10.1016\/j.bioorg.2020.103662","article-title":"Synthesis of New 4-Butyl-Arylpiperazine-3-(1H-Indol-3-Yl)Pyrrolidine-2,5-Dione Derivatives and Evaluation for Their 5-HT1A and D2 Receptor Affinity and Serotonin Transporter Inhibition","volume":"97","author":"Chodkowski","year":"2020","journal-title":"Bioorg. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Abram, M., Jakubiec, M., Rapacz, A., Mogilski, S., Latacz, G., Kami\u0144ski, R.M., and Kami\u0144ski, K. (2020). The Search for New Anticonvulsants in a Group of (2,5-Dioxopyrrolidin-1-Yl)(Phenyl)Acetamides with Hybrid Structure\u2014Synthesis and In Vivo\/In Vitro Studies. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228780"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8565","DOI":"10.1021\/acs.jmedchem.7b01114","article-title":"Multifunctional Hybrid Compounds Derived from 2-(2,5-Dioxopyrrolidin-1-Yl)-3-Methoxypropanamides with Anticonvulsant and Antinociceptive Properties","volume":"60","author":"Abram","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5274","DOI":"10.1021\/acs.jmedchem.5b00578","article-title":"Design, Synthesis, and Anticonvulsant Activity of New Hybrid Compounds Derived from 2-(2,5-Dioxopyrrolidin-1-Yl)Propanamides and 2-(2,5-Dioxopyrrolidin-1-Yl)Butanamides","volume":"58","author":"Zagaja","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.bmc.2015.12.027","article-title":"New Hybrid Molecules with Anticonvulsant and Antinociceptive Activity Derived from 3-Methyl- or 3,3-Dimethyl-1-[1-Oxo-1-(4-Phenylpiperazin-1-Yl)Propan-2-Yl]Pyrrolidine-2,5-Diones","volume":"24","author":"Zagaja","year":"2016","journal-title":"Bioorganic Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.seizure.2011.01.003","article-title":"Critical Review of Current Animal Models of Seizures and Epilepsy Used in the Discovery and Development of New Antiepileptic Drugs","volume":"20","year":"2011","journal-title":"Seizure"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1358\/mf.2009.31.2.1338414","article-title":"The Maximal Electroshock Seizure (MES) Model in the Preclinical Assessment of Potential New Antiepileptic Drugs","volume":"31","author":"Alves","year":"2009","journal-title":"Methods Find. Exp. Clin. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/epi.12893","article-title":"Genetic Background of Mice Strongly Influences Treatment Resistance in the 6 Hz Seizure Model","volume":"56","author":"Leclercq","year":"2015","journal-title":"Epilepsia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.seizure.2016.11.022","article-title":"Drug Development for Refractory Epilepsy: The Past 25 Years and Beyond","volume":"44","author":"Golyala","year":"2017","journal-title":"Seizure"},{"key":"ref_20","first-page":"99","article-title":"A Simplified Method of Evaluating Dose-Effect Experiments","volume":"96","author":"Litchfield","year":"1949","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.nurt.2006.11.009","article-title":"Discovery of Antiepileptic Drugs","volume":"4","author":"Smith","year":"2007","journal-title":"Neurotherapeutics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1111\/epi.13764","article-title":"Development and Pharmacological Characterization of the Rat 6 Hz Model of Partial Seizures","volume":"58","author":"Metcalf","year":"2017","journal-title":"Epilepsia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/epi.12296","article-title":"Issues Related to Development of New Anti-Seizure Treatments","volume":"54","author":"Wilcox","year":"2013","journal-title":"Epilepsia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1007\/s40263-021-00827-8","article-title":"The Pharmacology and Clinical Efficacy of Antiseizure Medications: From Bromide Salts to Cenobamate and Beyond","volume":"35","author":"Klein","year":"2021","journal-title":"CNS Drugs"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s12035-014-8775-9","article-title":"Specific Binding of Lacosamide to Collapsin Response Mediator Protein 2 (CRMP2) and Direct Impairment of Its Canonical Function: Implications for the Therapeutic Potential of Lacosamide","volume":"51","author":"Wilson","year":"2015","journal-title":"Mol. Neurobiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.taap.2017.04.010","article-title":"Increased Seizure Susceptibility and Other Toxicity Symptoms Following Acute Sulforaphane Treatment in Mice","volume":"326","author":"Nieoczym","year":"2017","journal-title":"Toxicol Appl. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ejphar.2017.01.018","article-title":"Formalin Injection Produces Long-Lasting Hypersensitivity with Characteristics of Neuropathic Pain","volume":"797","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1630709","DOI":"10.1155\/2018\/1630709","article-title":"Gaps in Understanding Mechanism and Lack of Treatments: Potential Use of a Nonhuman Primate Model of Oxaliplatin-Induced Neuropathic Pain","volume":"2018","author":"Hama","year":"2018","journal-title":"Pain Res. Manag."},{"key":"ref_29","first-page":"1744806917750995","article-title":"Down-Regulation of Kv4.3 Channels and a-Type K+ Currents in V2 Trigeminal Ganglion Neurons of Rats Following Oxaliplatin Treatment","volume":"14","author":"Ling","year":"2018","journal-title":"Mol. Pain"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"112743","DOI":"10.1016\/j.ejmech.2020.112743","article-title":"Rational Design of New Multitarget Histamine H3 Receptor Ligands as Potential Candidates for Treatment of Alzheimer\u2019s Disease","volume":"207","author":"Bajda","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s00011-016-0997-z","article-title":"Aryl-1,3,5-Triazine Ligands of Histamine H4 Receptor Attenuate Inflammatory and Nociceptive Response to Carrageen, Zymosan and Lipopolysaccharide","volume":"66","author":"Mogilski","year":"2017","journal-title":"Inflamm. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1016\/j.bmc.2019.02.020","article-title":"Alkyl Derivatives of 1,3,5-Triazine as Histamine H4 Receptor Ligands","volume":"27","author":"Mogilski","year":"2019","journal-title":"Bioorganic Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s40122-017-0091-4","article-title":"Pharmacotherapy for Neuropathic Pain: A Review","volume":"6","author":"Fornasari","year":"2017","journal-title":"Pain Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2174\/1570159X13666150216222543","article-title":"TRPV1 Channel: A Potential Drug Target for Treating Epilepsy","volume":"13","year":"2015","journal-title":"Curr. Neuropharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.eplepsyres.2016.02.005","article-title":"Involvement of TRPV1 Channels in the Activity of the Cannabinoid WIN 55,212-2 in an Acute Rat Model of Temporal Lobe Epilepsy","volume":"122","author":"Carletti","year":"2016","journal-title":"Epilepsy Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7093","DOI":"10.1021\/jm501981g","article-title":"Voltage-Gated Sodium Channels: Structure, Function, Pharmacology, and Clinical Indications","volume":"58","author":"Kraus","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1111\/bph.13747","article-title":"Calcium Signalling through L-type Calcium Channels: Role in Pathophysiology of Spinal Nociceptive Transmission","volume":"175","author":"Radwani","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"410","DOI":"10.3389\/fcell.2021.611773","article-title":"Functional Importance of Transient Receptor Potential (TRP) Channels in Neurological Disorders","volume":"9","author":"Lee","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S0920-1211(01)00302-3","article-title":"Pharmacological Characterization of the 6 Hz Psychomotor Seizure Model of Partial Epilepsy","volume":"47","author":"Barton","year":"2001","journal-title":"Epilepsy Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6607","DOI":"10.1113\/JP272725","article-title":"Cav1.2 and Cav1.3 L-type Calcium Channels Independently Control Short- and Long-term Sensitization to Pain","volume":"594","author":"Radwani","year":"2016","journal-title":"J. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1002\/med.21427","article-title":"Medicinal Chemistry, Pharmacology, and Clinical Implications of TRPV1 Receptor Antagonists","volume":"37","author":"Baraldi","year":"2017","journal-title":"Med. Res. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5507","DOI":"10.1073\/pnas.0407346102","article-title":"Genetic Predictors of the Maximum Doses Patients Receive during Clinical Use of the Anti-Epileptic Drugs Carbamazepine and Phenytoin","volume":"102","author":"Tate","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1111\/j.0013-9580.2004.12704.x","article-title":"Phenobarbital for the Treatment of Epilepsy in the 21st Century: A Critical Review","volume":"45","author":"Kwan","year":"2004","journal-title":"Epilepsia"},{"key":"ref_44","first-page":"698","article-title":"Human CYP2C9 and CYP2A6 Mediate Formation of the Hepatotoxin 4-Ene-Valproic Acid","volume":"283","author":"Sadeque","year":"1997","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/clpt.1983.8","article-title":"Single-Dose Kinetics and Metabolism of Carbamazepine-10,11-Epoxide","volume":"33","author":"Tomson","year":"1983","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1016\/0024-3205(96)00449-3","article-title":"A Novel Class of 5-HT2A Receptor Antagonists: Aryl Aminoguanidines","volume":"59","author":"Bryant","year":"1996","journal-title":"Life Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1021\/acschemneuro.8b00476","article-title":"KA-11, a Novel Pyrrolidine-2,5-Dione Derived Broad-Spectrum Anticonvulsant: Its Antiepileptogenic, Antinociceptive Properties and in Vitro Characterization","volume":"10","author":"Mogilski","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Andres-Mach, M., Szewczyk, A., Zagaja, M., Szala-Rycaj, J., Lemieszek, M.K., Maj, M., Abram, M., and Kaminski, K. (2021). Preclinical Assessment of a New Hybrid Compound C11 Efficacy on Neurogenesis and Cognitive Functions after Pilocarpine Induced Status Epilepticus in Mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063240"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.eplepsyres.2009.06.003","article-title":"Isobolographic Characterization of Interactions of Levetiracetam with the Various Antiepileptic Drugs in the Mouse 6 Hz Psychomotor Seizure Model","volume":"86","author":"Wojda","year":"2009","journal-title":"Epilepsy Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1002\/jps.3030460119","article-title":"The Pharmacological Activity of a Series of Basic Esters of Mono- and Dialkylmalonic Acids","volume":"46","author":"Dunham","year":"1957","journal-title":"J. Am. Pharm. Assoc. Am. Pharm. Assoc."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.pbb.2015.03.019","article-title":"Antinociceptive, Anti-Inflammatory and Smooth Muscle Relaxant Activities of the Pyrrolo[3,4-d]Pyridazinone Derivatives: Possible Mechanisms of Action","volume":"133","author":"Mogilski","year":"2015","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.bbrc.2017.07.109","article-title":"Valproic Acid Inhibits TTX-Resistant Sodium Currents in Prefrontal Cortex Pyramidal Neurons","volume":"491","author":"Szulczyk","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/23\/13092\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:39:25Z","timestamp":1760168365000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/23\/13092"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,3]]},"references-count":52,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["ijms222313092"],"URL":"https:\/\/doi.org\/10.3390\/ijms222313092","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,3]]}}}