title: Characterization of the anxiolytic and sedative profile of JM-20: a novel benzodiazepine-dihydropyridine hybrid molecule.
abstract: OBJECTIVE
  The aim of this study was to investigate the effects of oral administration of a novel benzodiazepine derivative, JM-20, on the neurological behavior of different rodent models, focusing on the GABAergic effect. We have also investigated the acute toxicity of oral administration of JM-20 in mice.
  
  
  METHODS
  Mice or rats received oral administration of JM-20 at 2, 4, 8, and 10 mg/kg to evaluate the sedative/hypnotic, anxiolytic, and anticonvulsant effects, as well as the influence on the stereotyped behavior induced by amphetamine. Diazepam (DZP) was used as a positive control. In addition, the mice received a single oral JM-20 dose of 2000 mg/kg to evaluate the acute toxicity.
  
  
  RESULTS
  In a dose-dependent manner, JM-20 (i) increased the number of crossings and decreased the number of rearings in the open-field test; (ii) decreased the aggressive behavior of socially-isolated mice; and (iii) increased the latency period for tonic seizure's onset and the percentage of survival of animals with seizures. Moreover, JM-20 increased the sleeping time induced by barbiturates and the time spent and the number of entries in the open arms of the elevated plus-maze test. In the JM-20 toxicity test, no mortality was observed and only minor signs of toxicity associated with sedation were detected.
  
  
  CONCLUSIONS
  These results indicate that JM-20 has an anxiolytic profile similar to DZP and its dihydropyridine moiety did not appear to interfere with the GABAergic activity associated with benzodiazepine. Furthermore, JM-20 did not show significant acute toxic effects in mice.
authors: Centro de Investigación y Desarrollo de Medicamentos, Ciudad Habana, Cuba.
authors: Yanier Nuñez
authors: YN
authors: Figueredo
authors: Estael Ochoa
authors: EO
authors: Rodríguez
authors: Yamila Verdecia
authors: YV
authors: Reyes
authors: Carmen Carrillo
authors: CC
authors: Domínguez
authors: Alicia Lagarto
authors: AL
authors: Parra
authors: Jeney Ramirez
authors: JR
authors: Sánchez
authors: René Delgado
authors: RD
authors: Hernández
authors: Marlene Porto
authors: MP
authors: Verdecia
authors: Gilberto L
authors: GL
authors: Pardo Andreu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000633:toxicity; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects*; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D003975:Diazepam / Q000494:pharmacology; D004095:Dihydropyridines / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D005260:Female; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D051379:Mice; D009525:Niacin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D051381:Rats
chemical_list: C000591456:3-ethoxycarbonyl-2-methyl-4-(2-nitrophenyl)-4,11-dihydro-1H-pyrido(2,3-b)(1,5)benzodiazepine; D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D004095:Dihydropyridines; D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; D009525:Niacin; C038806:1,4-dihydropyridine; D003975:Diazepam