Anticonvulsant and Toxicological Evaluation of ParafluorinatedChlorinated Derivatives of 3-Hydroxy-3-ethyl-3-phenylpropionamide
Joint Authors
Correa Basurto, Jose
Garrido-Acosta, Osvaldo
Meza-Toledo, Sergio E.
Anguiano-Robledo, Liliana
Soriano-Ursúa, Marvin A.
Davood, Asghar
Chamorro-Cevallos, Germán
Source
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-02-24
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
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 and Cl-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— G A B A A 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 62.0 mg/kg, respectively, and 66.4, 43.5, and in the PTZ seizure model 43.5 mg/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 G A B A A 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.
American Psychological Association (APA)
Garrido-Acosta, Osvaldo& Meza-Toledo, Sergio E.& Anguiano-Robledo, Liliana& Soriano-Ursúa, Marvin A.& Correa Basurto, Jose& Davood, Asghar…[et al.]. 2016. Anticonvulsant and Toxicological Evaluation of ParafluorinatedChlorinated Derivatives of 3-Hydroxy-3-ethyl-3-phenylpropionamide. BioMed Research International،Vol. 2016, no. 2016, pp.1-10.
https://search.emarefa.net/detail/BIM-1097590
Modern Language Association (MLA)
Garrido-Acosta, Osvaldo…[et al.]. Anticonvulsant and Toxicological Evaluation of ParafluorinatedChlorinated Derivatives of 3-Hydroxy-3-ethyl-3-phenylpropionamide. BioMed Research International No. 2016 (2016), pp.1-10.
https://search.emarefa.net/detail/BIM-1097590
American Medical Association (AMA)
Garrido-Acosta, Osvaldo& Meza-Toledo, Sergio E.& Anguiano-Robledo, Liliana& Soriano-Ursúa, Marvin A.& Correa Basurto, Jose& Davood, Asghar…[et al.]. Anticonvulsant and Toxicological Evaluation of ParafluorinatedChlorinated Derivatives of 3-Hydroxy-3-ethyl-3-phenylpropionamide. BioMed Research International. 2016. Vol. 2016, no. 2016, pp.1-10.
https://search.emarefa.net/detail/BIM-1097590
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1097590