title: SB 334867, a selective orexin receptor type 1 antagonist, elevates seizure threshold in mice.
abstract: OBJECTIVE
  Orexins A and B are hypothalamic neuropeptides involved in a number of physiological and behavioral processes. They work via OX1 and OX2 receptors. Recent studies revealed that orexins may be implicated in seizure activity. Therefore, the present study was undertaken to evaluate the influence of SB 334867 (a selective OX1 receptor antagonist) and EMPA (a selective OX2 receptor antagonist) on the seizure thresholds in mice. We also aimed to determine the changes of orexin A level following different types of seizures.
  
  
  METHODS
  The intravenous pentylenetetrazole (i.v. PTZ) seizure test, the maximal electroshock seizure threshold (MEST) test and the 6 Hz seizure test were used in the present study. Brain orexin A level was determined via enzyme-linked immunoassay (ELISA).
  
  
  RESULTS
  SB 334867 did not affect the seizure threshold for myoclonic twitches and tonic seizures in the i.v. PTZ seizure test. This compound, however, significantly raised the threshold for the PTZ-induced clonic seizures, for tonic hindlimb extension in the MEST test as well as for psychomotor seizures induced by 6 Hz stimulation. In comparison, EMPA did not alter the seizure thresholds in the i.v. PTZ test. Both EMPA and SB 334867 did not affect motor coordination and muscular strength. ELISA showed the increase of total brain orexin A level following different types of seizures.
  
  
  CONCLUSIONS
  Our results provide further evidence for the role of orexins in seizure activity and suggest that pharmacological blockade of the OX1 receptors may represent a novel therapeutic approach in the treatment of seizure disorders.
authors.affiliation: Department of Animal Physiology, Institute of Biology and Biochemistry, Maria Curie-Skłodowska University, Lublin, Poland. Electronic address: ksocala@op.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Socała
authors.affiliation: Department of Virology and Immunology, Institute of Microbiology and Biotechnology, Maria Curie-Skłodowska University, Lublin, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Szuster-Ciesielska
authors.affiliation: Department of Animal Physiology, Institute of Biology and Biochemistry, Maria Curie-Skłodowska University, Lublin, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Wlaź
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001583:Benzoxazoles / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D003292:Convulsants; D004597:Electroshock; D008297:Male; D051379:Mice; D053580:Muscle Strength / Q000187:drug effects; D009207:Myoclonus / Q000139:chemically induced / Q000503:physiopathology; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists / Q000494:pharmacology*; D064446:Orexin Receptors / Q000187:drug effects*; D000068797:Orexins / Q000378:metabolism; D010433:Pentylenetetrazole; D011597:Psychomotor Performance / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D000927:Anticonvulsants; D001583:Benzoxazoles; D003292:Convulsants; C497459:Hcrtr1 protein, mouse; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D000068797:Orexins; D014508:Urea; D010433:Pentylenetetrazole
keywords: 6Hz seizures; Maximal electroshock; Orexin A; Orexin receptors; Pentylenetetrazole