Minocycline- and tetracycline-class antibiotics are protective against partial seizures in vivo

Abstract

IntroductionIncreasing 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. MethodsWe 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. ResultsMinocycline, doxycycline and tetracycline showed anticonvulsant effects in abolishing partial seizures in the mouse 6-Hz seizure test. A dose-dependent effect was found, with ED50 of 170mg/kg for minocycline, 157mg/kg for doxycycline, and 255mg/kg for tetracycline with peak onset at 0.5h. At high doses, minocycline (250mg/kg) and doxycycline (150mg/kg) also had toxic effects, from motor impairments to respiratory failure and death. These drugs had no effects on the MES and scMET tests. ConclusionsIn 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.