fa In silico Screening and Evaluation of the Anticonvulsant Activity of Docosahexaenoic Acid-Like Molecules in Experimental Models of Seizures Related Fields Related Fields مقاله کامل Full Length/Original Article <p><strong>Background:</strong> Resistance to antiepileptic drugs as well as intolerability in 20-30% of the patients raises demand for developing new drugs with improved efficacy and safety. Acceptable anticonvulsant activity, good tolerability, and inexpensiveness of docosahexaenoic acid (DHA), make it as a good candidate for designing and development of the new anticonvulsant medications. <strong>Methods:</strong> Ten DHA-based molecules were screened based on <em>in silico</em> screening of DHA-like molecules by root-mean-square deviation of atomic positions, biological activity score of Professional Association for SQL Server and structural requirements suggested by pharmacophore design. Anticonvulsant activity of compounds were tested against clonic seizures induced by pentylenetetrazole (PTZ, 60 mg/kg, i.p.) and tonic seizures induced by maximal electroshock (MES, 50 mA, 50 Hz, 1 ms duration) by intracerebroventricular (i.c.v.) injection to mice. <strong>Results:</strong> Among screened compounds, 4-Phenylbutyric acid,<br> 4-Biphenylacetic acid, phenylacetic acid, and 2-Phenylbutyric acid showed significant protective activity in PTZ test with ED₅₀ values of 4, 5, 78, and 70 mM, respectively. In MES test, shikimic acid and 4-tert-Butylcyclo-hexanecarboxylic acid showed significant activity with ED₅₀ values 29 and 637 mM, respectively. Effective compounds had no mortality in mice up to the maximum i.c.v. injectable dose of 1 mM. <strong>Conclusion:</strong> Common electrochemical features and 3-dimensional spatial structures of the effective compounds suggest involvement of the anticonvulsant mechanisms similar to the parent compound DHA.&nbsp;</p> Epilepsy, Drug screening, Pentylenetetrazole (PTZ), Maximal electroshock (MES) 32 39 http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-1-626&slc_lang=fa&sid=1 Ali Gharibi Loron No Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran Soroush Sardari No Drug Design and Bioinformatics Unit, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran Jamshid Narenjkar No Department of Pharmacology and Biochemistry, School of Medicine, Shahed University, Tehran, Iran Mohammad Sayyah sayyahm2@pasteur.ac.ir Yes Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran