The Experts below are selected from a list of 306 Experts worldwide ranked by ideXlab platform
Meir Bialer - One of the best experts on this subject based on the ideXlab platform.
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Pharmacokinetic analysis and Anticonvulsant Activity of glycine and glycinamide derivatives
Epilepsy research, 1999Co-Authors: Sherbel Sussan, Arie Dagan, Meir BialerAbstract:The objective of this study was to investigate the pharmacokinetics and pharmacodynamics (Anticonvulsant Activity and neurotoxicity) of a series of amide derivatives of glycinamide in order to explore their structure pharmacokinetic-pharmacodynamic relationship and to discover a glycinamide derivative which might have the potential to become a new antiepileptic agent. The following compounds were investigated: glycylglycine, glycylglycinamide, gaboylglycinamide, N-acetylglycine, N-acetylglycinamide, N-acetylglycylglycinamide, N-acetyl, N'-benzylglycinamide, N-benzyloxycarbonylglycine or Z-glycine, Z-glycinamide, Z-glycylglycine and Z-glycylglycinamide. The Anticonvulsant Activity and neurotoxicity study was carried out in classical animal models for Anticonvulsant screening. The pharmacokinetics of the active compounds was studied in dogs, which is a common animal model for a comparative crossover pharmacokinetic studies. Of the compounds investigated in this study, all the dipeptides of glycinamide and the glycine derivatives were found to be inactive. The only two active compounds were: N-acetyl,N'-benzylglycinamide (VII) and Z-glycinamide (IX). These compounds demonstrated similar pharmacokinetic profiles. Unlike glycine or glycinamide, compounds VII and IX, being lipophilic derivatives of glycinamide, showed Anticonvulsant Activity in animal models due to their better pharmacodynamic and pharmacokinetic properties. The pharmacodynamics and pharmacokinetics of compounds VII and IX were similar to that of the potential new antiepileptics; N-valproylglycinamide and phthaloylglycinamide. This study provides certain clues concerning the structural requirements for the design of Anticonvulsant-active glycine derivatives.
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Pharmacokinetic analysis and Anticonvulsant Activity of two polyesteric prodrugs of valproic acid.
Biopharmaceutics & drug disposition, 1993Co-Authors: Salim Hadad, Tom B. Vree, Eppo Van Der Kleijn, Meir BialerAbstract:The pharmacokinetics of the following two polyesteric prodrugs of valproic acid (VPA) have been investigated: 1,4-butanediol divaiproate (BDV) and glyceryl trivalproate (GTV). In addition, the Anticonvulsant Activity of these compounds has been evaluated and compared to that of VPA and valpromide (VPD). Valproic acid, and its two esteric derivatives were administered intravenously to six dogs at an equivalent dose (400 mg VPA) and their pharmacokinetics investigated. In the case of BDV, the biotransformation to VPA was complete, but in the case of GTV, it was only partial. Of the two investigated esteric prodrugs of VPA, only BDV demonstrated Anticonvulsant Activity and showed less neurotoxicity than VPA and VPD, and therefore had a better protective index. The Anticonvulsant Activity is explained on pharmacokinetic and pharmacodynamic grounds due to its complete conversion to VPA and the possible synergism in Anticonvulsant Activity between VPA and 1,4-butanediol.
Zhe-shan Quan - One of the best experts on this subject based on the ideXlab platform.
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Synthesis and Anticonvulsant Activity of novel purine derivatives.
European journal of medicinal chemistry, 2014Co-Authors: Shi-ben Wang, Peng Jin, Zhe-shan QuanAbstract:A series of new purines containing triazole and other heterocycle substituents was synthesized and evaluated for their preliminary Anticonvulsant Activity and neurotoxicity by using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and rotarod neurotoxicity (TOX) tests. Among the compounds studied, 9-decyl-6-(1H-1,2,4-triazol-1-yl)-9H-purine (5e) was the most potent compound, with a median effective dose of 23.4 mg/kg and a high protective index of more than 25.6 after intraperitoneal administration in mice. Compound 5e showed significant oral Activity against MES-induced seizures in mice, with an ED50 of 39.4 mg/kg and a PI above 31.6. These results demonstrate that compound 5e possesses better Anticonvulsant Activity and is safer than the commercially available drugs carbamazepine and valproate in MES, scPTZ and TOX models.
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Design, Synthesis of 6-Substituted-pyrido[3,2-d]pyridazine Derivatives with Anticonvulsant Activity
Medicinal chemistry (Shariqah (United Arab Emirates)), 2012Co-Authors: Zheng-qi Dong, Xiao-mei Liu, Cheng-xi Wei, Zhe-shan QuanAbstract:Aim to find new compounds with stronger Anticonvulsant Activity and lower neurotoxicity, a novel series of 6-substituted-pyrido[3,2-d]pyridazine derivatives was synthesized using furo[3,4-b]pyridine-5,7-dione as the starting material. We evaluated their Anticonvulsant Activity and neurotoxicity using by maximal electroshock (MES) and rotarod neurotoxicity (TOX) tests. The results showed that N-m-chlorophenyl-[1,2,4]triazolo- [4,3-b]-pyrido[3,2- d]pyridazin-6-amine (3) was the most potent Anticonvulsant, with ED50 value of 13.6 mg/kg and protective index ( PI = TD50/ED50) values of 7.2 in the MES test. Compound N-m-chlorophenyltetriazolo[5,1-b]-pyrido[3,2-d]pyridazin-6-amine (19), exhibited significant Anticonvulsant Activity in maximal electroshock test with PI value of 13.4, which was safer than marketed drug carbamazepine.
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Characterization of the Anticonvulsant Activity of doxepin in various experimental seizure models in mice
Pharmacological Reports, 2009Co-Authors: Lei Zhang, Hu-ri Piao, Zhe-shan QuanAbstract:Abstract In this paper, the Anticonvulsant characteristics of doxepin were evaluated in numerous experimental seizure models, including maximal electroshock (MES)-, pentylenetetrazole (PTZ)-, isoniazid (ISO)-, 3-mercaptopropionic acid (3-MP)-, bicuculline (BIC)-, thiosemicarbazide (THIO)-, and strychnine (STR)-induced seizures. In addition, the acute adverse-effect profile of doxepin with respect to impairment of motor coordination was assessed with a mouse rotarod test. The evaluation of the time-course and doseresponse relationships for doxepin provided evidence that the peak maximum Anticonvulsant Activity and acute adverse effects occurred 5 min after intraperitoneal ( ip ) administration. The results also revealed that doxepin had excellent Anticonvulsant Activity against maximal electroshock-induced seizures in mice with a median effect value (ED 50 ) of 6.6 mg/kg. The assessment of acute adverse effects in the rotarod test revealed that doxepin induced acute neurotoxicity, and its median toxic dose (TD 50 ) was 26.4 mg/kg. Additionally, doxepin showed Anticonvulsant Activity in several chemically-induced seizure models, including ISO, 3-MP, BIC, and THI. Based on this study, we can conclude that the antidepressant drug doxepin may be useful for treatment of depression in patients with epilepsy due to its short time to peak maximum Anticonvulsant Activity after ip administration (5 min) and remarkable Anticonvulsant Activity (6.6 mg/kg).
Safinaz E Abbas - One of the best experts on this subject based on the ideXlab platform.
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synthesis and Anticonvulsant Activity of some quinazolin 4 3h one derivatives
Molecules, 2008Co-Authors: Hanan H Georgey, Nagwa M Abdelgawad, Safinaz E AbbasAbstract:A number of 3-substituted-2-(substituted-phenoxymethyl) quinazolin-4(3H)-one derivatives 4a,b, 5a-c, 6, 7a-f, 8a-e and 9a,b have been synthesized. Their structures have been elucidated on the basis of elemental analyses and spectroscopic studies (IR, 1H-NMR, MS). A preliminary evaluation of the Anticonvulsant Activity of the prepared compounds has indicated that compounds 4b, 7b-f, 8a and 9b exhibit significant Anticonvulsant Activity, while compounds 6, 8b and 8d show mild to moderate Activity.
Prashant J Burange - One of the best experts on this subject based on the ideXlab platform.
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synthesis and Anticonvulsant Activity of clubbed thiazolidinone barbituric acid and thiazolidinone triazole derivatives
Arkivoc, 2007Co-Authors: Mahendra Shiradkar, Mangesh Ghodake, Kailash G Bothara, Shashikant V Bhandari, Ana Nikalje, Kalyan Chakravarthy Akula, Nisheeth C Desai, Prashant J BurangeAbstract:A new series of clubbed thiazolidinone-barbituric acid and thiazolidinone-triazole derivatives was synthesized to study the effect of a hydrophobic unit, hydrogen bonding domain and electron-donor group on the compounds' Anticonvulsant Activity. The structures of the synthesized compounds were confirmed by their spectroscopic data and elemental analysis. All compounds were evaluated for their Anticonvulsant Activity in two animal models of seizures, viz. maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). The compounds were also evaluated for neurotoxicity. Compounds 4g, 4i, 5g and 5i exhibited excellent Anticonvulsant Activity in both animal models of seizure.
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Synthesis and Anticonvulsant Activity of clubbed thiazolidinone–barbituric acid and thiazolidinone–triazole derivatives
Arkivoc, 2007Co-Authors: Mahendra Shiradkar, Mangesh Ghodake, Kailash G Bothara, Shashikant V Bhandari, Ana Nikalje, Kalyan Chakravarthy Akula, Nisheeth C Desai, Prashant J BurangeAbstract:A new series of clubbed thiazolidinone-barbituric acid and thiazolidinone-triazole derivatives was synthesized to study the effect of a hydrophobic unit, hydrogen bonding domain and electron-donor group on the compounds' Anticonvulsant Activity. The structures of the synthesized compounds were confirmed by their spectroscopic data and elemental analysis. All compounds were evaluated for their Anticonvulsant Activity in two animal models of seizures, viz. maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). The compounds were also evaluated for neurotoxicity. Compounds 4g, 4i, 5g and 5i exhibited excellent Anticonvulsant Activity in both animal models of seizure.
Salim Hadad - One of the best experts on this subject based on the ideXlab platform.
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Pharmacokinetic analysis and Anticonvulsant Activity of two polyesteric prodrugs of valproic acid.
Biopharmaceutics & drug disposition, 1993Co-Authors: Salim Hadad, Tom B. Vree, Eppo Van Der Kleijn, Meir BialerAbstract:The pharmacokinetics of the following two polyesteric prodrugs of valproic acid (VPA) have been investigated: 1,4-butanediol divaiproate (BDV) and glyceryl trivalproate (GTV). In addition, the Anticonvulsant Activity of these compounds has been evaluated and compared to that of VPA and valpromide (VPD). Valproic acid, and its two esteric derivatives were administered intravenously to six dogs at an equivalent dose (400 mg VPA) and their pharmacokinetics investigated. In the case of BDV, the biotransformation to VPA was complete, but in the case of GTV, it was only partial. Of the two investigated esteric prodrugs of VPA, only BDV demonstrated Anticonvulsant Activity and showed less neurotoxicity than VPA and VPD, and therefore had a better protective index. The Anticonvulsant Activity is explained on pharmacokinetic and pharmacodynamic grounds due to its complete conversion to VPA and the possible synergism in Anticonvulsant Activity between VPA and 1,4-butanediol.