Anticonvulsant and Toxicological Evaluation of Parafluorinated/Chlorinated Derivatives of 3-Hydroxy-3-ethyl-3-phenylpropionamide.
Although the anticonvulsant activity of 3-hydroxy-3-ethyl-3-phenylproionamide (HEPP) is well-known, its use is limited by the pharmacotoxicological profile. We herein tested its fluorinated and chlorinated derivatives (F-HEPP andCl-HEPP)with two seizure models, maximal electroshock seizures (MES), a...
| Publicado en: | BioMed Research International Vol. 2016; pp. 1 - 11 |
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| Autores principales: | , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
1/1/2016
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=128194467&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 128194467 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 1/1/2016 vid: 2016 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 128194467 128194467 128194467 10.1155/2016/3978010 128194467 ppf: 1 ppct: 10 formats: fmt: @attributes: type: P tig: atl: Anticonvulsant and Toxicological Evaluation of Parafluorinated/Chlorinated Derivatives of 3-Hydroxy-3-ethyl-3-phenylpropionamide. aug: au: Garrido-Acosta, Osvaldo Meza-Toledo, Sergio E. Anguiano-Robledo, Liliana Soriano-Ursúa, Marvin A. Correa-Basurto, José Davood, Asghar Chamorro-Cevallos, Germán affil: Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, 15500 México City, DF, Mexico sug: subj: Anticonvulsants Pharmacodynamics Receptors, Cell Surface Drug Effects Toxicity Tests Evaluation Seizures Drug Therapy Electroshock Azepines Administration and Dosage Administration, Intraperitoneal Animal Studies Computer Simulation Phenytoin Administration and Dosage Mice Anticonvulsants Administration and Dosage Noxae Anticonvulsants Therapeutic Use Drug Toxicity ab: Although the anticonvulsant activity of 3-hydroxy-3-ethyl-3-phenylproionamide (HEPP) is well-known, its use is limited by the pharmacotoxicological profile. We herein tested its fluorinated and chlorinated derivatives (F-HEPP andCl-HEPP)with two seizure models, maximal electroshock seizures (MES), and intraperitoneal pentylenetetrazole (PTZ) administration. Neurotoxicity was examined via the rotarod test. With in silico methods, binding was probed on possible protein targets--GABAA receptors and the sodium channel Nav1.2. The median effective doses (ED50) of HEPP, F-HEPP, and Cl-HEPP in the MES seizure model were 129.6, 87.1, and 62.0mg/kg, respectively, and 66.4, 43.5, and in the PTZ seizure model 43.5mg/kg. The HEPP-induced neurotoxic effect, which occurred at twice the ED50 against MES (p < 0.05), did not occur with F-HEPP or Cl-HEPP. Docking studies revealed that all tested ligands bound to GABAA receptors on a site near to the benzodiazepine binding site. However, on the sodium channel open pore Nav1.2, R-HEPP had interactions similar to those reported for phenytoin, while its enantiomer and the ligands F-HEPP and Cl-HEPP reached a site that could disrupt the passage of sodium. Our results show that, as anticonvulsant agents, parahalogen substituted compounds have an advantageous pharmacotoxicological profile compared to their precursor. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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