Use of a new antiepileptic drug or an old one as first drug for treatment of absence epilepsy

Penovich, Patricia; Willmore, L. James

doi:10.1111/j.1528-1167.2009.02234.x

Cited by 30 publications

(17 citation statements)

References 80 publications

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“…Antiepileptic drugs (AEDs) can control seizures to some extent; however, about 30% of epilepsy patients are thought to be undertreated . Many currently available AEDs also have serious side effects , and in general, patients require lifelong medication. This has resulted in a continuous challenge for us to find new antiepileptic agents with more selectivity and lower toxicity.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Anticonvulsant Activity Evaluation of 4‐Phenyl‐[1,2,4]triazolo[4,3‐a]quinazolin‐5(4H)‐one and Its Derivatives

Zhang

Jin

Wang

et al. 2015

Archiv der Pharmazie

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A series of 4-(substituted-phenyl)-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-ones (6a-x) with triazole and other heterocyclic substituents (7-14) were synthesized and the compounds were evaluated for their anticonvulsant activity and neurotoxicity by maximal electroshock (MES) and rotarod neurotoxicity tests. Among the compounds studied, 6o and 6q showed wide margins of safety with protective indices (PIs) that were much higher than those of currently used drugs (PI6o > 25.5, PI6q > 26.0). Compounds 6o and 6q showed significant oral activity against MES-induced seizures in mice, with ED50 values of 88.02 and 94.6 mg/kg, respectively. The two compounds were also found to have potent activity against seizures that were induced by pentylenetetrazole and bicuculline.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Anticonvulsant Activity Evaluation of 4‐Phenyl‐[1,2,4]triazolo[4,3‐a]quinazolin‐5(4H)‐one and Its Derivatives

Zhang

Jin

Wang

et al. 2015

Archiv der Pharmazie

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“…Conventional antiepileptic agents (i.e., phenytoin and carbamazepine) and recent antiepileptic drugs (i.e., gabapentin, vigabatrin, remacemide, and loreclezole) are clinically effective for different seizure types. However, only 50% of sufferers are adequately treated with the currently available antiepileptic drugs (AEDs), and a few AEDs have severe side effects [3][4][5][6][7]. Therefore, the development of safer and more effective AEDs is necessary.…”

Section: Introductionmentioning

confidence: 99%

Experimental and Theoretical Studies of the Vibrational and Electronic Properties of (2E)-2-[3-(1H-imidazol-1-yl)-1-phenyl-propylidene]-N-phenylhydrazinecarboxamide: An Anticonvulsant Agent

2015

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In the current investigation, the molecular structure of the anticonvulsant agent (2E)-2-[3-(1H-imidazol-1-yl)-1-phenylpropylidene]-N-phenylhydrazinecarboxamide ((2E)-HIPC) was theoretically modelled using ab initio Hartree-Fock (HF) and density functional theory (DFT/B3LYP) calculations. The Fourier transform (FT) infrared and FT-Raman spectra of (2E)-HIPC were also recorded, and the observed bands were assigned to the vibrational normal modes. The main functional groups were identified via vibrational analysis, and their absorption bands were assigned. A comparative analysis was performed for the computed and experimental results. Subtle differences were observed between the calculated and experimental UV-Vis spectra. Time-dependent density functional theory (TD-DFT) excitation energies were calculated for five excited electronic OPEN ACCESSAppl. Sci. 2015, 5 956 states. The calculations were applied to simulate the spectra of (2E)-HIPC, and these simulated spectra exhibited excellent agreement with the experimental spectra. The DFT/B3LYP/6-311++G(d,p) method, after scaling, exhibited better agreement with the experimental values than the results obtained by the HF method. The energy, oscillator strength, and wavelength computed by TD-DFT (IEFPCM) are consistent with the experimental results. The molecular electrostatic potential (MEP) and frontier molecular orbitals (HOMO-LUMO) were also determined to enable prediction of the structural changes and reactive sites. Mulliken population charges of the title molecule were also calculated in the gas phase. The NMR chemical shifts ( 13 C and 1 H) were calculated using the gauge-including atomic orbital method and the B3LYP/6-311++G(d,p) approach and were compared with the experimental values.

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“…Considering that ethosuximide has been indicated for therapeutic use in humans (Browne et al, 1975;Katzung, 2007;Wheless et al, 2007;Penovich and Willmore, 2009), despite the abovementioned side effects that it may produce, it seems necessary to test its cytotoxic and genotoxic potential on human cells. An in vitro lymphocyte assay to investigate micronucleus formation would be applicable, as this test has been widely recommended for studies of the cytotoxicity and genotoxicity of drugs (Preston et al, 1987;Fenech, 2007).…”

Section: Introductionmentioning

confidence: 99%

Micronucleus formation, proliferative status, cell death and DNA damage in ethosuximide-treated human lymphocytes

Ghiraldini

Mello

2010

Cell Biology Int. Rep

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Cite this article as: Ghiraldini FG and Mello MLS (2010) Micronucleus formation, proliferative status, cell death and DNA damage in ethosuximidetreated human lymphocytes. Cell Biol. Int. Rep. 17(1):art:e00006. AbstractEthosuximide is a T-type Ca 2+ channel blocker that has been used as an anticonvulsant to treat absence seizures. Because no data have yet been reported on the cytotoxicity, genotoxicity and cell death effects of this drug, we have investigated ethosuximide-treated human lymphocytes with Fenech's CBMN (cytochalasin-blocked micronucleus cytome) assay and single-cell gel electrophoresis (comet assay). The tests allowed us to examine micronucleus formation, the proliferative status of the viable cells, nuclear blebbing, nucleoplasmic bridge formation, cell death (CBMN assay) and DNA damage (comet assay). The lymphocytes were treated for 24 h with 25, 50 or 100 mg/ml ethosuximide. The cells used for the CBMN assay were examined either immediately or 24 h after the cytochalasin blockade. For the comet assay, cells were examined immediately or 22 h after 2 h ethosuximide treatment. The results indicate that 25 and 50 mg/ml ethosuximide did not induce micronucleus formation, nuclear abnormalities, cell death or DNA damage, nor did they affect cell proliferation, suggesting no cytotoxic or genotoxic effects under such experimental conditions. However, under treatment with 100 mg/ml ethosuximide, an increase in micronucleus formation and nuclear abnormalities, but a decrease in cell proliferation and in DNA damage, and no change in the cell death ratio, were detected. Although apparently contradictory, the data obtained with the 100 mg/ml concentration may indicate that induction of cytotoxicity and genotoxicity are not to be disregarded when considering this drug concentration. The mechanisms underlying the cellular response to ethosuximide remain to be explored.

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Use of a new antiepileptic drug or an old one as first drug for treatment of absence epilepsy

Cited by 30 publications

References 80 publications

Synthesis and Anticonvulsant Activity Evaluation of 4‐Phenyl‐[1,2,4]triazolo[4,3‐a]quinazolin‐5(4H)‐one and Its Derivatives

Synthesis and Anticonvulsant Activity Evaluation of 4‐Phenyl‐[1,2,4]triazolo[4,3‐a]quinazolin‐5(4H)‐one and Its Derivatives

Experimental and Theoretical Studies of the Vibrational and Electronic Properties of (2E)-2-[3-(1H-imidazol-1-yl)-1-phenyl-propylidene]-N-phenylhydrazinecarboxamide: An Anticonvulsant Agent

Micronucleus formation, proliferative status, cell death and DNA damage in ethosuximide-treated human lymphocytes

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