title: Adaptation of Lorke's method to determine and compare ED50 values: the cases of two anticonvulsants drugs.
abstract: BACKGROUND
  We determined the median effective dose (ED50) values for the anticonvulsants phenobarbital and sodium valproate using a modification of Lorke's method. This modification allowed appropriate statistical analysis and the use of a smaller number of mice per compound tested.
  
  
  METHODS
  The anticonvulsant activities of phenobarbital and sodium valproate were evaluated in male CD1 mice by maximal electroshock (MES) and intraperitoneal administration of pentylenetetrazole (PTZ). The anticonvulsant ED50 values were obtained through modifications of Lorke's method that involved changes in the selection of the three first doses in the initial test and the fourth dose in the second test. Furthermore, a test was added to evaluate the ED50 calculated by the modified Lorke's method, allowing statistical analysis of the data and determination of the confidence limits for ED50.
  
  
  RESULTS
  The ED50 for phenobarbital against MES- and PTZ-induced seizures was 16.3mg/kg and 12.7mg/kg, respectively. The sodium valproate values were 261.2mg/kg and 159.7mg/kg, respectively.
  
  
  CONCLUSIONS
  These results are similar to those found using the traditional methods of finding ED50, suggesting that the modifications made to Lorke's method generate equal results using fewer mice while increasing confidence in the statistical analysis. This adaptation of Lorke's method can be used to determine median letal dose (LD50) or ED50 for compounds with other pharmacological activities.
authors.affiliation: Departamento de Farmacia. Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala s/n, Col. Plutarco Elías Calles, C.P. 11340, México, D.F., Mexico. Electronic address: osvaldo_ga81@yahoo.com.mx.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Garrido-Acosta
authors.affiliation: Departamento de Bioquímica. Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala s/n, Col. Plutarco Elías Calles, C.P. 11340, México, D.F., Mexico.
authors.forename: Sergio Enrique
authors.initials: SE
authors.lastname: Meza-Toledo
authors.affiliation: Sección de Estudios de Posgrado e Investigación Laboratorio de Farmacología Molecular, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomás, C.P. 11340, México, D.F., Mexico.
authors.forename: Liliana
authors.initials: L
authors.lastname: Anguiano-Robledo
authors.affiliation: Sección de Estudios de Posgrado e Investigación Laboratorio de Farmacología Molecular, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomás, C.P. 11340, México, D.F., Mexico.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Valencia-Hernández
authors.affiliation: Departamento de Farmacia. Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala s/n, Col. Plutarco Elías Calles, C.P. 11340, México, D.F., Mexico.
authors.forename: Germán
authors.initials: G
authors.lastname: Chamorro-Cevallos
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004597:Electroshock / Q000379:methods; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology*; D012640:Seizures / Q000188:drug therapy*; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid; D010433:Pentylenetetrazole; D010634:Phenobarbital
keywords: ED(50); LD(50); Lorke; Maximal electroshock; Methods; Pentilentetrazole; Phenobarbital; Sodium valproate