title: Minocycline- and tetracycline-class antibiotics are protective against partial seizures in vivo.
abstract: BACKGROUND
  Increasing evidence suggests the role of inflammation in enhancing neuronal excitability and contributing to epileptogenesis. Tetracycline-class antibiotics minocycline, doxycycline and tetracycline have been shown to have anti-apoptotic and anti-inflammatory effects.
  
  
  METHODS
  We investigated the anti-seizure effects of tetracycline-class antibiotics minocycline, doxycycline and tetracycline in vivo by using the maximal electric shock (MES), 6-Hz (minimal clonic seizure) test and subcutaneous Metrazol (scMET) models of epilepsy.
  
  
  RESULTS
  Minocycline, doxycycline and tetracycline showed anticonvulsant effects in abolishing partial seizures in the mouse 6-Hz seizure test. A dose-dependent effect was found, with ED(50) of 170 mg/kg for minocycline, 157 mg/kg for doxycycline, and 255 mg/kg for tetracycline with peak onset at 0.5h. At high doses, minocycline (250 mg/kg) and doxycycline (150 mg/kg) also had toxic effects, from motor impairments to respiratory failure and death. These drugs had no effects on the MES and scMET tests.
  
  
  CONCLUSIONS
  In the three tests of anti-seizure activity, minocycline, doxycycline, and tetracycline were found to be protective in one: the 6-Hz seizure model. Our data suggest that minocycline and other tetracycline-class drugs may offer some degree of anticonvulsant effect in the setting of CNS disease trials.
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, CA 94143-0112, USA. WangD@neurosurg.ucsf.edu
authors.forename: Doris D
authors.initials: DD
authors.lastname: Wang
authors.forename: Dario J
authors.initials: DJ
authors.lastname: Englot
authors.forename: Paul A
authors.initials: PA
authors.lastname: Garcia
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lawton
authors.forename: William L
authors.initials: WL
authors.lastname: Young
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology / Q000627:therapeutic use*; D004828:Epilepsies, Partial / Q000188:drug therapy / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use*; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000188:drug therapy / Q000517:prevention & control*; D013752:Tetracycline / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D000927:Anticonvulsants; D013752:Tetracycline; D008911:Minocycline; D004318:Doxycycline